Drug delivery system and method of use

ABSTRACT

A drug delivery system is disclosed that includes a drug delivery device having a reservoir and a delivery cannula having a proximal end in fluid communication with the reservoir and a distal end to be received within a patient. The drug delivery system may further include one or more sensors coupled to the drug delivery device, a wireless transmitter, and a controller coupled to the one or more sensors and the wireless transmitter. The controller may be configured to use the one or more sensors to determine a condition or an operational state of the drug delivery device, and control the wireless transmitter to wirelessly transmit one or more reports representative of the condition or the operational state of the drug delivery device. A method for use with a drug delivery device is also disclosed.

CROSS-REFERENCE TO RELATED APPLICATION

The priority benefit of U.S. Provisional Patent Application No.62/007,007, filed Jun. 3, 2014, is claimed, and the entire contentsthereof are expressly incorporated herein by reference.

BACKGROUND

This patent is directed to systems and methods for use with drugdelivery devices relating to control of the drug delivery devices andcommunication of information obtained from the drug delivery devices.

Drugs can be administered through the use of drug delivery devices, suchas autoinjectors or on-body injectors or infusers. These devices mayreplace older delivery systems using the combination of a syringe and avial of the drug or medicament, or a pre-filled syringe. Autoinjectorsand on-body injectors may be used to automate the injection and deliveryor administration process, thereby simplifying the process for certainpatient groups or sub-groups for which use of the syringe/vialcombination or pre-filled syringe systems would be disadvantageous,whether because of physiological or psychological impediments.

Even with the use of drug delivery devices, such as autoinjectors,patients may experience challenges during the initial use of the drugdelivery device after they have been prescribed a drug that is deliveredor administered through the use of a drug delivery device. For example,the user may be uncertain whether the medication inside the drugdelivery device is the medication prescribed for them. Additionally, theuser may be uncertain whether the medication has expired. Further, theuser may be uncertain whether the injection should be delayed after adrug delivery device has been removed from cold storage, such as in arefrigerator, and if the injection should be delayed, how long it shouldbe delayed. The user may also be uncertain if the actions and theirsequence correctly operate the drug delivery device. Even if the correctactions are performed in the correct sequence, the user may be uncertainthe drug has been completely delivered, such that the injection iscomplete.

Other patients may experience challenges in being adherent or compliantwith the treatment regimen. For example, certain patients may notperform the injections according to the treatment regimen, havingforgotten to perform the injection at all. Other patients may performthe injections, but then be unable to remember whether they performedthe injections because they become distracted before they are able torecord that they did so. Some patients may elect not to perform theinjections because of misunderstandings or miscommunications of when orhow the medication will affect the patient's disease or symptoms,especially where the effects are not felt by the patient until aconsiderable portion of the treatment regimen has been performed. Somepatients may require support and/or encouragement from others(healthcare provider, caregiver, family member, etc.), which supportand/or encouragement cannot be provided because the people that wouldprovide that support and/or encouragement do not know if the patient hasperformed the treatment or if the treatment regimen has been followedcorrectly.

In addition, the condition and use of drug delivery devices is ofimportance to other parties, such as drug device manufacturers,pharmacies, health care providers and insurers. For instance,information regarding the condition of the drug delivery device alongthe supply chain may be relevant to whether the drug delivery devicewill be in good working order when it arrives for use with the patient.Information regarding the location of the drug delivery device along thesupply chain may be relevant to the manufacturer and the pharmacy toensure that adequate supplies are available for the pharmacy to deliveryto the user. The compliance information mentioned above may be importantto the healthcare providers and insurers, as well as to the patient,because compliance with a therapy regimen may have a direct impact onthe success of the therapy.

As set forth in more detail below, the present disclosure sets forth andrug delivery system embodying advantageous alternatives to existingdrug delivery devices and that may address one or more of the challengesor needs mentioned above.

SUMMARY

According to an aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir and a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient. The drug deliverysystem also includes one or more sensors coupled to the drug deliverydevice, a wireless transmitter, and a controller coupled to the one ormore sensors and the wireless transmitter. The controller may beconfigured to: use the one or more sensors to determine a condition oran operational state of the drug delivery device, and control thewireless transmitter to wirelessly transmit one or more reportsrepresentative of the condition or the operational state of the drugdelivery device.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and a removablesterile barrier disposed about the distal end of the delivery cannula.The drug delivery system also includes a first sensor configured todetect movement of the removable sterile barrier, a wirelesstransmitter, and a controller coupled to the first sensor and thewireless transmitter. The controller may be configured to: use the firstsensor to determine if the removable sterile barrier has been removedfrom the distal end of the delivery cannula, and control the wirelesstransmitter to wirelessly transmit a report representative of removal ofthe removable sterile barrier if the removable sterile barrier has beenremoved from the distal end of the delivery cannula.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and an actuatorconfigured to trigger the drug delivery device. The drug delivery systemalso includes first sensor configured to detect movement of theactuator, a wireless transmitter, and a controller coupled to the firstsensor and the wireless transmitter. The controller may be configuredto: use the first sensor to determine if the actuator has been used totrigger the drug delivery device, and control the wireless transmitterto wirelessly transmit a report representative of triggering of the drugdelivery device if the actuator has been used.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and a needle shieldmoveable relative to the distal end of the delivery cannula. The drugdelivery system also includes a first sensor configured to detectmovement of the needle shield, a wireless transmitter, and a controllercoupled to the first sensor and the wireless transmitter. The controllermay be configured to: use the first sensor to determine if the needleshield has been moved relative to the distal end of the deliverycannula, and control the wireless transmitter to wirelessly transmit areport representative of insertion of the distal end of the deliverycannula into the patient if the needle shield has been moved relative tothe distal end of the delivery cannula.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and a needle shieldmoveable relative to the distal end of the delivery cannula. The drugdelivery system also includes a first sensor configured to detectmovement of the needle shield, a wireless transmitter, and a controllercoupled to the first sensor and the wireless transmitter. The controllermay be configured to: use the first sensor to determine if the needleshield is disposed about the distal end of the delivery cannula, andcontrol the wireless transmitter to wirelessly transmit a reportrepresentative of a completion of a delivery of a medicament from thereservoir to the patient if the needle shield is disposed about thedistal end of the delivery cannula

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and a plunger moveablethrough the reservoir to discharge a medicament from the reservoir. Thedrug delivery system also includes a first sensor configured to detectmovement of the plunger, a wireless transmitter, and a controllercoupled to the first sensor and the wireless transmitter. The controllermay be configured to: use the first sensor to determine if the plungerhas completed a delivery stroke, and control the wireless transmitter towirelessly transmit a report representative of a completion of adelivery of a medicament from the reservoir to the patient if the needleshield is disposed about the distal end of the delivery cannula.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and a plunger moveablethrough the reservoir to discharge a medicament from the reservoir. Thedrug delivery system also includes a first sensor configured to detectmovement of the plunger, a wireless transmitter, and a controllercoupled to the first sensor and the wireless transmitter. The controllermay be configured to: use the first sensor to determine a traveldistance of the plunger, and control the wireless transmitter towirelessly transmit a report representative of an amount of medicamentdelivered to the patient from the reservoir based on the travel distanceof the plunger.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir and a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient. The drug deliverysystem also includes a first sensor configured to detect presence orabsence of fluid within the reservoir, a wireless transmitter, and acontroller coupled to the first sensor and the wireless transmitter. Thecontroller may be configured to: use the first sensor to determine anamount of medicament remaining in the reservoir, and control thewireless transmitter to wirelessly transmit a report representative ofan amount of medicament delivered to the patient from the reservoirbased on the amount of medicament remaining in the reservoir.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir, a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient, and an housing havingan opening for the distal end of the delivery cannula. The drug deliverysystem also includes a first sensor configured to detect contact betweenthe housing and an object, a wireless transmitter, and a controllercoupled to the first sensor and the wireless transmitter. The controllermay be configured to: use the first sensor to determine if the housingcontacts the patient, and control the wireless transmitter to wirelesslytransmit a report representative of contact between the housing and thepatient.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a reservoir and a deliverycannula having a proximal end in fluid communication with the reservoirand a distal end to be received within a patient. The drug deliverysystem also includes a first sensor configured to detect a temperatureof a medicament within the reservoir, a wireless transmitter, and acontroller coupled to the first sensor and the wireless transmitter. Thecontroller may be configured to: use the first sensor to determine ifthe temperature of the medicament is greater than or less than athreshold temperature, and control the wireless transmitter towirelessly transmit a report representative of a suitability of themedicament for delivery to the patient.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a drug delivery devicecomprising a reservoir and a delivery cannula having a proximal end influid communication with the reservoir and a distal end to be receivedwithin a patient. The drug delivery system also includes a first sensorconfigured to detect a geographic location of the drug delivery device,a wireless transmitter, and a controller coupled to the first sensor andthe wireless transmitter. The controller may be configured to: use thefirst sensor to determine the geographic location of the drug deliverydevice, and control the wireless transmitter to wirelessly transmit areport representative of the geographic location of the drug deliverydevice.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a drug delivery devicecomprising a reservoir and a delivery cannula having a proximal end influid communication with the reservoir and a distal end to be receivedwithin a patient. The drug delivery system also includes a first sensorconfigured to detect an orientation of the delivery cannula, a wirelesstransmitter, and a controller coupled to the first sensor and thewireless transmitter. The controller may be configured to: use the firstsensor to determine if the delivery cannula is oriented for deliveringmedicament in the reservoir to the patient, and control the wirelesstransmitter to wirelessly transmit a report representative of a properor improper orientation of the delivery cannula for delivering themedicament to the patient.

According to another aspect of the disclosure, a drug delivery systemincludes a drug delivery device comprising a drug delivery devicecomprising a reservoir, a delivery cannula having a proximal end influid communication with the reservoir and a distal end to be receivedwithin a patient, and a battery. The drug delivery system also includesa first sensor configured to detect a charge level of the battery, awireless transmitter, and a controller coupled to the first sensor andthe wireless transmitter. The controller may be configured to: use thefirst sensor to determine the charge level of the battery, and controlthe wireless transmitter to wirelessly transmit a report representativeof the charge level of the battery.

According to a further aspect of the disclosure, a method is provided ofusing a drug delivery system comprising a reservoir, a delivery cannulahaving a proximal end in fluid communication with the reservoir and adistal end to be received within a patient, and a removable sterilebarrier disposed about the second end of the delivery cannula. Themethod includes determining if the removable sterile barrier has beenremoved from the distal end of the delivery cannula, and transmitting areport representative of the removal of the removable sterile barrier ifthe removable sterile barrier has been removed from the distal end ofthe delivery cannula.

BRIEF DESCRIPTION OF THE DRAWINGS

It is believed that the disclosure will be more fully understood fromthe following description taken in conjunction with the accompanyingdrawings. Some of the figures may have been simplified by the omissionof selected elements for the purpose of more clearly showing otherelements. Such omissions of elements in some figures are not necessarilyindicative of the presence or absence of particular elements in any ofthe exemplary embodiments, except as may be explicitly delineated in thecorresponding written description. None of the drawings are necessarilyto scale.

FIG. 1 is a schematic diagram of a drug delivery system according anembodiment of the disclosure in communication with one or more computingdevices and one or more networks;

FIG. 2 is a block diagram of a method of operating the drug deliverysystem illustrated in FIG. 1 according to an embodiment of thedisclosure;

FIGS. 3A-3C is a block diagram of a method of operating the drugdelivery system illustrated in FIG. 1 according to another embodiment ofthe disclosure;

FIG. 4 is a block diagram of a method of operating a computing devicesuch as is illustrated in FIG. 1 according to an embodiment of thedisclosure, the computing device in communication with a drug deliverysystem operating according to one of the methods disclosed herein, forexample;

FIG. 5 is a block diagram of a method of operating a drug deliverysystem according to another embodiment of the disclosure;

FIG. 6 is a block diagram of a method of operating a drug deliverysystem according to a still further embodiment of the disclosure;

FIG. 7 is a block diagram of a method of operating a computing deviceaccording to an embodiment of the disclosure, the computing device incommunication with the drug delivery system operating according to themethod of FIG. 6, for example;

FIG. 8 is a block diagram of a method carried out by a drug deliverysystem according to another embodiment of the disclosure;

FIG. 9 is a partial cross-sectional view illustrating an embodiment of asystem used to carry out the method of FIG. 8;

FIG. 10 is a block diagram of a method carried out by a drug deliverysystem according to yet another embodiment of the disclosure;

FIG. 11 is a block diagram of a method carried out by a drug deliverysystem according to a further embodiment of the disclosure;

FIGS. 12A and 12B are schematic views of an embodiment of a system usedto carry out the method of FIG. 11;

FIG. 13 is a cross-sectional view of an embodiment of a drug deliverysystem including an autoinjector;

FIG. 13A is a cross-sectional view of an alternative cannula subassemblyfor the drug delivery system of FIG. 13;

FIG. 14 is a perspective view of an embodiment of a drug delivery systemincluding an on-body injector;

FIG. 15 is a cross-sectional view of the drug delivery device of FIG. 14taken along line 15-15;

FIG. 16 is a cross-sectional view of the drug delivery device of FIG. 14taken along line 16-16;

FIG. 17 is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector;

FIG. 18a is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector;

FIG. 18b is a top view of a needle shield of the autoinjector of FIG.18a arranged in a distal position;

FIG. 18c is a top view of the needle shield of the autoinjector of FIG.18a arranged in a proximal position;

FIG. 19 is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector;

FIG. 20 is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector;

FIG. 21a is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector in a state where delivery of amedicament is not complete;

FIG. 21b is a cross-sectional view of the drug delivery system of FIG.21a in a state where delivery of the medicament is partially complete;

FIG. 21c is a cross-sectional view of the drug delivery system of FIG.21a in a state where delivery of the medicament is complete;

FIG. 22a is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector in a state where delivery of amedicament is not complete;

FIG. 22b is a cross-sectional view of the drug delivery system of FIG.22a in a state where delivery of the medicament is complete;

FIG. 22c is an enlarged view of a sensor used in the drug deliverysystem of FIGS. 22a and 22 b;

FIG. 23a is a cross-sectional view of another embodiment of drugdelivery system including an autoinjector;

FIG. 23b is a circuit diagram depicting a controller and a sensor usedby the drug delivery system of FIG. 23 a;

FIG. 24a is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector in a state where delivery of amedicament is not complete;

FIG. 24b is a cross-sectional view of the drug delivery system of FIG.24a in a state where delivery of the medicament is complete;

FIG. 25a is a cross-sectional view of another embodiment of drugdelivery system including an autoinjector in a state where delivery of amedicament is not complete;

FIG. 25b is a cross-sectional view of the drug delivery system of FIG.25a in a state where delivery of the medicament is complete;

FIG. 26a is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector in a state where delivery of amedicament is not complete;

FIG. 26b is a cross-sectional view of the autoinjector of FIG. 26a alongline B-B;

FIG. 27c is a cross-sectional view of the drug delivery system of FIG.26a in a state where delivery of the medicament is partially complete;

FIG. 27d is a cross-sectional view of the drug delivery system of FIG.26a in a state where delivery of the medicament is complete;

FIG. 27e is a circuit diagram depicting a controller and a sensor usedby the drug delivery system of FIGS. 27a -d;

FIG. 28 is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector;

FIG. 29a is a cross-sectional view of another embodiment of a drugdelivery system including an autoinjector prior to contact with apatient;

FIG. 29b is a cross-sectional view of the drug delivery system of FIG.29a during contact with a patient;

FIG. 30a is a perspective view of another embodiment of a drug deliverysystem including an on-body injector;

FIG. 30b is another perspective view the drug delivery system of FIG. 30a;

FIG. 31 is a perspective view of a drug delivery system according to afurther embodiment of the disclosure including an anti-roll removablesterile barrier;

FIG. 32 is an assembly view of the anti-roll removable sterile barrierof FIG. 31.

FIG. 33 is cross-sectional view of an embodiment of a removable sterilebarrier attached to a housing of a drug delivery device; and

FIG. 34 is a cross-sectional view of the removable sterile barrier ofFIG. 32 after its removal from the housing of the drug delivery device.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

This disclosure is directed to a plurality of systems including a drugdelivery device, and to a plurality of methods for using the drugdelivery system. In particular, the systems and methods involve thedetermination of one or more states, which states may be determinedthrough the use of one or more sensors in combination with one or morecontrollers. The sensors may rely on mechanical, electrical or chemicalsensing mechanisms, and the controllers may be mechanical, electrical orelectro-mechanical. By way of example and not by way of limitation, thestates may relate to the operation of the drug delivery device, or tothe condition of the drug delivery device. The system and methods mayuse the state determination to control the operation of the drugdelivery device, and/or may communicate the state determination to otherdevices, such as third-party servers that may collect, process and/orfurther disseminate the state determinations received from the systemincluding the drug delivery device, the one or more sensors, and the oneor more controllers. In addition or in the alternative, the systems andmethods may communicate the state determination to local devices, suchas a mobile computing device (e.g., cell phone).

A drug delivery system according to the disclosure may include a drugdelivery device having a reservoir (which may also be referred to as aprimary container, e.g. a syringe, vial or cartridge). The reservoir maycontain a drug, which may also be referred to as a medication or amedicament. The drug may be, but is not limited to various biologicalssuch as peptides, peptibodies, or antibodies. The drug may be in a fluidor liquid form, although the disclosure is not limited to a particularstate (e.g., no differentiation is intended between a solution, a gel,or a lyophilized product for example). The drug delivery device alsoincludes delivery cannula having a first end connected to or connectablein fluid communication with the reservoir and a second end to beinserted within a patient. As used herein, the term “delivery cannula”or “cannula” is hereby defined to mean a tube that can be inserted intothe body for the delivery of fluid. A cannula may include a rigid orsemi-rigid needle or blunt cannula, or may be in a flexible form, byexample and not by way of limitation. The cannula may be integrated withthe other elements of the drug delivery device, or the cannula may beseparate from the other elements of the drug delivery until immediatelyprior to use. According to certain embodiments, the drug delivery devicemay further include an inserter to introduce the second end into thepatient, although this is not required according to each embodiment ofthe disclosure. The inserter may or may not be withdrawn back into thedevice, thereby leaving the cannula in a patient.

Considering the foregoing description of the drug delivery device, thedevice may be characterized as an autoinjector or an on-body injector orinfuser (the reference to injector intended to include also a referenceto an infuser, to the extent that a difference is suggested).Autoinjectors may be single-use devices, administering a single doseduring a single application of the device to the user's skin, althoughautoinjectors are not limited to only single-use devices—they may bemulti-use devices as well. On-body injectors may be multi-use devices,administering multiple doses during one or more applications of thedevice to the user's skin, although on-body devices may also be used assingle-use devices. Either autoinjectors or on-body injectors may haveassemblies or sub-assemblies that are reusable, in that the assembliesmay be used and re-used by refilling the reservoir, by removing an emptyreservoir and replacing it with a filled reservoir, or by replacing thecannula, for example.

As noted above, the system or method according to the disclosure willdetermine one or more states relative to the drug delivery device.

For example, the system or method may determine if the drug deliverydevice is in one or more operational states (i.e., a state relating tothe operation of the drug delivery device to deliver the drug to thepatient). A non-exhaustive list of the general operational states mayinclude (i) packaged/ready for distribution; (ii) packaged/distributed;(iii) unpackaged/ready for administration; (iv) sterile barrier removed;(v) device applied; (vi) cannula injected (or inserted); (vii) drugdelivery initiated; (viii) drug delivery completed; and (ix) deviceremoved. The system or method may determine specific operational stateswithin each of the general operational states; for example, the systemor method may determine if plunger has been moved from a first end of abore (defining a drug reservoir) to a second end of the bore todetermine if the drug delivery device is in the “drug delivery complete”state.

Furthermore, the system or method may determine if the drug deliverydevice is in one or more condition states (i.e., a state relating to thecondition of the drug delivery device, not necessarily related to theoperation of the drug delivery device to deliver the drug to thepatient). A non-exhaustive list of condition states may include (i) age(e.g., taken with respect to a manufacturing date or an expirationdate); (ii) sterility/contamination; (iii) temperature (or temperaturehistory); and (iv) orientation. The determination of a condition statemay be considered as part of the determination of an operational state;for example, the determination of the temperature state may beconsidered as part of the determination of the “ready foradministration” state. Alternatively, the operational and conditionstates may be determined separately.

These states may be determined through the use of one or more sensors.The sensors may be particular to a condition state to be determined: forexample, a thermocouple disposed adjacent to the reservoir may be usedto determine the temperature state of the drug delivery device. Thesensors may be particular to an operational state to be determined: forexample, a switch may be coupled to a needle guard to determine when aneedle cap has been removed to determine the “sterile barrier removed”operational state, the switch being open when the needle cap is disposedover the second end of the cannula and the switch being closed when theneedle guard is not disposed over the second end of the cannula. Sensorsmay be used to determine both a condition state and an operationalstate: for example, the thermocouple may be used to determine thetemperature condition state of the device (or more particularly, thedrug), and/or the thermocouple may be used to determine the “ready foradministration” operational state.

The system or method may use the determined states to control theoperation of the drug delivery device. For example, the system mayinclude a controller that is coupled to the sensor and may be coupled toone or more of the assemblies or subassemblies of the drug deliverydevice described above, or to one or more additional assemblies orsubassemblies of the drug delivery device. The controller may be adaptedstructurally or programmed (if electrical or electro-mechanical) toactivate or to inhibit these assemblies or subassemblies in accordancewith the determined states. For example, the drug delivery device mayinclude a lockout that limits or completely inhibits the operation ofthe injector, and the controller may activate the lockout in areversible fashion if the temperature state of the drug delivery device(and in particular, the drug in the reservoir) is below a thresholdstate.

The system or method may communicate the determined state(s) to anotherdevice or system, which communication may be performed in conjunctionwith use of the determined state(s) to control the operation of the drugdelivery device. For example the system or method may communicate thedetermined state(s) with a networked device using a communication link.In this sense, a networked device is intended to include any device thatcommunicates with at least one other device over a communication link,and might include communication with a device such as mobile device(e.g., cell phone or mobile computing device) using a Bluetoothconnection or a computing device using a Wi-Fi connection, for example.The networked device may communicate the determined states to othercomputing devices remote from the drug delivery system over the networkthat includes the networked device such as a server. According tocertain embodiments of the present disclosure, the system communicatesdirectly with the network (i.e., without an intermediate networkeddevice—the system would be a networked device) or directly with a remotecomputing device such as a server (using, for example, a 3G antenna).The state information communicated over network, may then be used, forexample, to determine if a patient is in compliance, or if a class ofdrug delivery devices is exhibiting a systemic malfunction. The stateinformation may be used in other manners as well.

The systems and methods may also include control of the drug deliverydevice according to information relating to the identity of the drug,the drug delivery device, or the user, and/or communication of thisidentity information. Identity information relating to the drug mayinclude a drug name, a drug concentration, dose information, a lotnumber or serial number, and a date of manufacture and/or expiration.Identity information relating to the drug delivery device may include adevice type (e.g., autoinjector, on-body injector), a lot number orserial number, and a date of manufacture. Information relating to theuser may include a patient name, demographic information, and patientsubgroup information. This information may be referred to as “static”information, in contrast to the state information discussed above.

As to the communication of the information, and in particular relativeto the identity information discussed immediately above, it will berecognized that not all information may be useful, desired, or evenaccessible to every different party whether for convenience, patientprivacy or data security concerns.

FIG. 1 illustrates a drug delivery system 100 according to an embodimentof the disclosure. The drug delivery system 100 may be associated with apatient 102, who may use the drug delivery system 100 to inject a drugas part of a therapeutic regime. The drug delivery system 100 maycommunicate with a computing device (e.g. server) 104 via one or moreintermediate computing devices and/or one or more networks. In turn, theserver 104 may communicate with the drug delivery system 100, thepatient 102, and one or more computing devices (with their associatedparties) via one or more intermediate computing devices and/or one ormore networks. As is also illustrated in FIG. 1, the server 104 maycommunicate directly with the drug delivery system 100, using a 3Gantenna for example.

For example, the drug delivery system 100 is illustrated ascommunicating with a mobile computing device 110 (e.g., a smartphone)via a first communication link 112, and with a computing device (e.g., apersonal computer or dedicated hub) 114 via a second communication link116. Both links 112, 116 may operate according to a near fieldcommunication protocol, such as Bluetooth, for example. The mobilecomputing device 110 may communicate with a cellular network 118 via acommunication link 120, while the other computing device 114 maycommunicate with a hard-wired network (e.g., local area network or widearea network) 122 via a communication link 124. These networks 118, 122may also communicate with the server 104.

The networks 118, 122 may facilitate communication between the server104 and one or more parties associated with the patient 102, such as hisor her caregiver 130, support giver 132, and healthcare provider 134,via their mobile computing devices (e.g., smartphones). The server 104may also be in communication with one or more computing devices (e.g.,servers) associated with one or more additional parties associated withthe patient 102. For example, a healthcare system server 140, a paymentserver 142, a pharmacy server 144, a distributor server 146, and agovernmental agency server 148 are illustrated in communication with theserver 104 via the network 122. It will also be recognized that thenetworks 118, 122 may be in communication with each other.

FIG. 2 illustrates a method 200 of operating a drug delivery system,such as the drug delivery system 100 in FIG. 1, to determine variousstates of the drug delivery system, to control the drug delivery systemaccording to those states, and to communicate the determined stateinformation to a computing device, such as the mobile device 110 and/orthe server 104. From a brief review of the flowchart of FIG. 1, it willbe recognized that the method 200 according to FIG. 2 illustrates thedetermination of various operational states of the drug delivery devicethat is part of the drug delivery system, and the actions taken andcommunications made in association with or in regard to theseoperational states. It should also be recognized that while the method200 includes the actions described herein, other embodiments of a methodof operating a drug delivery system according to the disclosure mayinclude only some of the actions described herein, as is specificallyillustrated in FIG. 3, for example. Those actions outlined in FIG. 2 notincluded in other embodiments of a method of operating a drug deliverydevice according to the disclosure may be omitted or eliminated.

The actions and communications from the drug delivery system may changewith the drug delivery device operational state as that device passesthrough the useable product life cycle from manufacture to disposal, asindicated in FIG. 2. In fact, the determination made on the basis of asingle sensor may vary according to the drug delivery device'soperational state. By way of example, in regard to those drug deliverydevices that utilize a needle cap disposed over a second end of thecannula to preserve sterility, determination made using a needle capsensor that the needle cap has been removed from over or about thesecond end of the cannula prior to package or packaging removal mightindicate that primary container integrity has been compromised, whereasin removal or separation of the needle cap from over or about the secondend of the cannula after package or packing removal might indicate thatthe device is ready to administer the drug.

The method 200 starts at block 202, and continues from block 204 toblocks 206 and 208 when it is determined that the drug delivery systemhas been packaged. In particular, once it is determined that the deviceis packaged at block 204, a communication is made at block 206 to reportthe operational state change of the device, and the method continues toblock 208, where a determination is made whether the device has beendistributed.

Between the determination that the drug delivery system has beenpackaged and the determination that the drug delivery system has beendistributed to the user, the drug delivery device may pass throughdifferent portions of the supply chain. The portions of the supply chainthrough which the drug delivery system may pass may depend on the drugin the drug delivery device, the intended use of the drug deliverydevice by the user, which may be a patient or a healthcare professional,or other factors (such as the structure and characteristics of the drugdelivery device itself).

As the packaged device emerges from manufacture, there is interest inmaintaining current knowledge of the authenticity, environmental historyand information about the current or historic location throughoutdistribution. Consequently, while the method and system await thedetermination of the transition to the next operational state at block208, the system may monitor and communicate this information at block210. By automating the collection and reporting of information in thisstate, supply chain partners can leverage improved information andsupply chain management systems. Information such as productidentification, expiration date, and counterfeiting measures might beuseful for logistics, warehousing, and customs officials. Thisinformation, when added to what is known of the combination product(i.e., therapeutic and diagnostic products that combine drugs, devices,and/or biological products) during manufacture can help alert interestedand authorized parties to product location in the event of field eventssuch as product transfer or return and replacement under recall.

Depending on the route which the drug delivery system takes between themanufacturer and its distribution to the patient or healthcare provider,the drug delivery system may also pass through a pharmacy, where thesystem may also monitor and communicate information at block 210. If thedrug delivery system passes through a pharmacy, information such asdrug/dose/device, environmental history, expiration date, counterfeitingmeasures, and location data may provide useful information to thoseresponsible for managing stock and ensuring product quality as deliveredto the end user. Incorporation of signals which trigger access to labeland instruction information can provide value in training the end userabout the delivery device or drug product, provide access to usercommunities and provide an information stream to the user or user'snetwork about the effectiveness of product training or associatedmaterials. These signals, when added to what is known of the combinationproduct during manufacture can help to alert to product location in theevent of field events such as product transfer or return and replacementunder recall.

Once the determination is made at block 208 that the packaged producthas been distributed to the user (e.g., a patient or healthcareprovider), the method 200 may continue to block 212 where the change inthe operational state is communicated. The method 200 may continue witha determination as to whether the drug delivery device has beenunpackaged at block 214. If the determination has not been made that thedrug delivery device has been unpackaged, then the method 200 maymonitor the drug delivery system, and report information at block 216.If the determination has been made that the drug delivery device hasbeen unpackaged, then the method continues to block 218 with thecommunication of the operation state change.

During this operational state, information such as environmentalhistory, instructions for use, storage instructions, productauthenticity or any associated field alerts for the produced lot ofmaterials, expiration date, medication reminders and current location orestimated arrival through shipping provide information of interest tothe user. The use of sensors to provide signals for environmentalcondition such as temperature can help the user to understand whetherthe product is now suitable for use, i.e., whether the method may passfrom block 214 to block 220 (with the reporting occurring at block 218).One extended example of this is a “wake-up” of the electronics into ahigh activity state for delivery and reporting when temperatureexceeding a certain threshold such as 15C. This could result in amessage to the user (e.g., via the user's networked devices) to returnto the device to cold storage or administer within 24 hours. Similarly,the sensed temperature could put the electronics back into a low energy“sleep” if the drug product drops below a preset threshold such as 15C.

If the determination is made at block 214 that the device has beenunpackaged (presumably by the user), then the method 200 may report theoperational state change at block 218, and proceed to the determinationat block 220. As noted above, it is possible for the method to carry outdeterminations other than those illustrated at block 214 before themethod 200 may proceed to block 220.

In determining if the system is ready for use at block 220, it istypical to verify the quality of the product presented. While the usermay perform this action, the system may also include sensors that willcarry out this action. For example, the verifications may includeverification of the label information to confirm authenticity, visualinspection the device for signs of damage or to confirm that the needlecap has not come free in shipping, visual inspection of the drug productcontainer for color and clarity. The verifications may also include adetermination whether the environmental history of the device is suchthat the device may be safely used. Such a determination may considerthe environmental conditions through storage and distribution which mayhave compromised the drug product or the delivery device. By includingsensors in the device (such as position or proximity sensors for theneedle cap or temperature sensors), many of these inspection steps canbe automated, providing greater ease of use to the user and greaterinformation to the user and user's network.

According to the determination made at block 220, the method 200 maypass to block 222, where the user discards the device instead of usingthe device. For example, it may be determined at block 220 that theenvironmental history of the device is such that the device may not besafely used. In such a case, the device may indicate to the user thatthe device is to be discarded at block 222 and may communicate thisinformation to a remote server that tracks such device determinations,or may communicate this with a local device (such as a mobile or cellphone or other mobile device, portable computing device or the like)that is capable of being or is networked and may communicate theinformation to a remote server.

On the other hand, if the determination is made at block 220 that thesystem is ready for administration, the method 200 may proceed to block224 with the reporting of the change in operational state. The method200 may then continue to block 226, wherein a determination is madewhether a barrier is no longer intact, has prematurely deployed or if ithas been prematurely removed or separated from the drug delivery devicesuch that the sterility of the device is no longer preserved or can nolonger be assured to be preserved. In this regard, the barrier may be asterile barrier (i.e., the minimum package that prevents ingress ofmicroorganisms and allows aseptic presentation of the product at thepoint of use), such as a needle cap. If the determination is made atblock 226 that the barrier is intact, then the method 220 may continueat block 228, wherein the operational state and condition states of thesystem are monitored and that information is communicated to local orremote devices. If the determination is made that the barrier is nolonger intact, then the method 200 may continue to block 230, whereinthe operational change is reported, and the method 200 may continue toblock 232.

In regard to the determination made at block 226, it is typical forautoinjectors and on-body devices to have a component or packagingproduct that is removed immediately before administration that maintainsthe sterility of the needle or injection head. Sometimes outsideprotective packaging is inappropriately removed and discarded days inadvance of medicament administration; while normally the patient may beno more than a few minutes away from insertion and/or injection when thesterile barrier is removed from the device. This determination alsoprovides a key opportunity to ensure the drug delivery deviceelectronics are “awake” during the injection process without requiringexcess cost and bulk to ensure adequate power through manufacture,storage, and distribution before key functions are performed.

By triggering electronics to “wake-up” to a high activity state uponremoval of the sterile barrier, onboard electronics of a Smart DrugDelivery Device can provide significantly improved power consumptionwhile in manufacture, storage and distribution. According to certainembodiments, the startup sequence may take 10-200 seconds for example,inclusive of startup, completion of preliminary checks and interactionwith the patient/user in advance of attempted administration (whichinteraction may include waiting for the device/drug to warm to roomtemperature, although inclusion of this action may further increase thetotal time required). Conversely, one can wait for body contact ordelivery actuation to wake-up onboard electronics, but this is notlikely to provide an opportunity for every desired “Smart” feature.Similarly, if something such as original packaging removal is used towake-up the electronics then there is a risk that a significant amountof power will be utilized in advance of delivery that can complicate theoptimization of the device and drug delivery system.

It is possible to design a component that is removed in conjunction withthe sterile barrier, which has typically provided an opportunity toincrease the ease, ergonomics, or obviousness of removal. By designing atab, or other electrically insulating feature into this component; itmay be inserted into the power circuit of onboard electronics so thatremoval of the sterile barrier connects the battery or other powersupply and wakes up the electronics to perform the required functions.Alternatively, the removal of the barrier may cause a switch to close,completing a circuit with the power supply, and thus powering up thesystem.

At block 232, a determination is made if the drug delivery system hasbeen applied to the patient. In regard to an autoinjector, thisdetermination may involve a determination as to whether the autoinjectorhas been held in place against the patient's skin. In regard to anon-body injector, this determination may involve a determination as towhether an adhesive has been exposed on a surface of the on-bodyinjector and the injector has been disposed onto the surface of thepatient's skin. According to certain embodiments of the method 200, if adetermination is made at block 232 that the drug delivery system has notbeen applied within a specified time after the barrier is no longerintact, the user may be instructed to discard the device at block 234and the event is communicated to local and/or remote devices.Alternatively, if the determination is made that the device has beenapplied to the patient at block 232, the operational state change isreported at block 236 and the method 200 proceeds to block 238.

In some embodiments, the determination made at block 232 regarding skinapplication may be performed repeatedly at pre-defined intervals (e.g.,every 5 milliseconds) throughout the remainder of the method 200. Bydoing so, it may be possible to determine if the drug delivery devicehas been prematurely removed from the patient's skin prior to thecompletion of medicament delivery to the patient. Also, if prematureremoval has occurred, it may be possible to determine when it occurredrelative to the start of medicament delivery. The timing of thepremature removal may be used to calculate the actual amount of themedicament actually delivered to the patient prior to the removal of thedrug delivery device from the patient's skin.

As was the case above, it may also be useful to know when deliberatecontact has been made, because this may be a useful opportunity to“wake-up” onboard electronics from a low power state for exampledepending on what “smart” functions are desired by the circuitry.Alternatively, some checks to confirm that the device is ready foradministration might be performed in order to provide the user withgreater confidence in the value of the injection.

Additionally, there is a risk of deliberate non-compliance with therapywhere many commercially available injectors can be tricked intodispensing medication by depressing the needle guard and activating theproduct to dispense into the air instead of the patient. There isincremental value in the knowledge that the device was in contact withthe body throughout the delivery period, and particularly if additionalinformation that is in line with the properties expected of human tissueand appropriate injection sites. The overlap of known body contact withthe duration of drug delivery and completion can be used to infer theamount of dosage missed in the event of use errors as further explainedin the similar state of “needle inserted”.

The method 200 determines at block 238 if the second end of the cannulahas been injected or inserted into the patient. With many drug deliverydevices, the injection of the cannula into the patient is notinstantaneous with the application of the drug delivery device to thepatient's skin. For example, there may be a delay between applicationand injection because of time required for various assemblies orsubassemblies of the drug delivery device to recognize that the drugdelivery device has been applied and to activate the injector.Alternatively, there may be a planned delay in the injection of thecannula because the administration of the drug is planned to occur aftera time delay elapses after application of the drug delivery device toprevent damage to the cannula or discomfort to the patient because ofthe planned delay between application and injection. In yet anotheralternative, in an on-body drug delivery device, a needle referred to asan introducer needle may be activated to insert a cannula that canremain inserted in the patient. The needle then retracts back into thedelivery device, leaving the cannula behind. The actual injection orintroduction of a medicament can occur immediately thereafter or at alater desired time. As such, the method 200 may proceed to block 240 ifit is determined at block 238 that the cannula has not been inserted,and the system may monitor the operational state and one or morecondition states and communicate that information.

Similar to the body contact information, the injection information maybe used in conjunction with other processes to achieve a higherconfidence in the gathered information. In contrast to body contactinformation, accurately measuring needle insertion to the targetadministration route such as intradermal, subcutaneous, intramuscular,intravenous, ocular or others can provide direct confirmation that thedrug product was delivered to the correct anatomical depth and location.

One use for needle insertion signal can be release of a delivery lockoutonce the needle has been inserted into the patient. Alternatively, ifthe completion of drug delivery occurs and the needle was inserted forthe entire period of time between “delivery triggered” and “deliverycompletion” a very high degree of confidence in successful dosing isprovided. And conversely if the timing of the events do not overlapappropriately it may be possible to predict the amount of dose that wassuccessfully delivered based on the systems delivery characteristics. Inthe event that an incomplete or unsuccessful dose administration isdetected and reported, there is significant incremental value if theamount of dose discrepancy is also reported. A “Smart Drug DeliveryDevice” might be used for many different types of medicaments withvarying therapeutic effects and toxicity risk profiles. For example somemedications may require urgent completion of dosing such as by a secondinjection for any incomplete dose if there is a low risk of toxicity buthigh risk of complications with a missed or incomplete dose.Alternatively, a healthcare provider may prefer to know about a missedor incomplete dose but wait for the next dose instead of scheduling areplacement if the risk of complications is low. Importantly, there maybe opportunities to mitigate issues associated with incomplete dosing byadministering just the amount of missed dose if it is correctly recordedand reported, offering an opportunity to maximize benefit whileminimizing the overall cost of care.

If the determination is made at block 238 that the needle has beeninserted, then the method 200 may communicate the operation state changeat block 242 and determine if the administration of the drug has beeninitiated or triggered at block 244. If the cannula has been inserted,but the administration has not yet started, the method 200 may continueat block 246 to monitor the states of the drug delivery device, andcommunicate that information. A delay between the insertion of thecannula and the administration of the drug product may occur because ofthe sequential operation of the assemblies or subassemblies of the drugdelivery device, or the delay may be planned, such that the cannula isinserted into the patient contemporaneous with or approximatelycontemporaneous with the application of the device to the patient's skinbut administration occurs at least a time delay thereafter.

It is believed that successful triggering of delivery generally leads tosuccessful dosing except when a device may be programmed to insert acannula and then at a later time the injection of the medicament begins.Upon triggering, the patient has generally performed an action intendedto provide the therapeutic result. Triggering delivery may be viewed,according to certain embodiments, as evidence of a higher level ofcommitment as compared to body contact or needle insertion alone. It isbelieved that some patients try different sites by placing the deviceagainst the body to “feel” it before triggering delivery. Many devicesinclude a feature to ensure that delivery is not triggered for suchtrials. Thus it is known that triggering delivery typically indicatesthe patient has mentally committed to dose the prescribed therapy.Enabling features of a “Smart Drug Delivery Device” to sense whendelivery has been triggered provides value to many stakeholders as anindication of compliance. While not as direct a measure of successfuldelivery by comparison to other methods, detecting a trigger signal canbe achieved through relatively simple means, providing greater value ofcost and reliability.

Once the determination has been made that administration of the drugproduct has been initiated at block 244, the method may proceed to block248 where the operational state change of the device is communicatedwith local and/or remote devices. The method 200 then proceeds to block250, and a determination is made that the administration of the drugproduct is complete. Until the determination is made that theadministration of the drug product is complete, the system continues tomonitor the device, and communicate the information at block 252. Oncethe determination is made that administration is complete at block 250,the change in operational state is communicated at block 254, and themethod 200 proceeds to block 256.

Capturing the completion of administration or delivery is a usefulmetric, particularly in combination with other device state information.By itself there is value if a device does not have the means to captureother device states, and indeed would provide sufficient value to manystakeholders if the other states were unable to be reported. However,capturing the time and date of dose delivery completion in comparison toother device states can provide a very high level of confidence (orcounterevidence) that the drug was delivered successfully. For example,if dose completion occurred while the needle was still inserted thatconfirms that the patient or caregiver administering the medicament didnot pull the device away from the body during or after it was triggeredthus compromising the dosage accuracy. Commonly available drug deliverydevices may lockout to prevent drug delivery in advance of applying thedevice to the body, but once the device has been applied to the bodythere is generally no means of keeping the device secured against thebody during the full time of delivery. Most often the drug will continueto deliver, spilling into the air as waste if the needle is pulled awayfrom the body after the delivery is triggered. Sometimes a medicamentmay be painful or cause a certain sensation due to the specificingredients or speed of delivery and thus cause a reflex thatcompromises the dose even after the needle has been inserted. Othertimes, an action of the delivery device itself may startle the user andcause the same reflex. It is known to be important for the user oruser's network to understand the difference between slow response andnoncompliance to a therapy in order to provide the patient with theevidence needed to encourage compliance with a given therapy or theevidence needed to alter a therapeutic strategy. Thus there isincredible value to the patient to a comprehensive measurement andreporting of drug delivery device performance.

Several of the embodiments disclosed below may be expanded in scope tomonitor the overall progress of the delivery. For example if an opticalsensor is optimized to detect the stopper material and oriented at theend of the delivery stroke that can be used to relay completioninformation; similarly an array of optical sensors placed parallel tothe travel of a plunger through a drug reservoir might be used tomonitor progress throughout the travel.

At block 256, the method 200 determines if the device has been removedfrom the patient. The determination at block 256 may be based on a skinsensor that determines if the device is no longer in contact with thepatient's skin. According to other embodiments, the determination may bemade on a needle shield or other structure that deploys after removalfrom the skin to prevent contact with the second end of the cannula ofthe drug delivery device. According to still other embodiments, theremoval of the drug delivery device may be based on a change in theorientation of the drug delivery device. In any event, until it isdetermined that the drug delivery device has been removed, the methodand system may monitor the device at block 258 and communicateinformation with local and/or remote devices. When it is determined thatthe drug delivery device has been removed, the method communicates thisoperational state change at block 260, and ends at block 262.

Disposal of the device, and alternatively receipt of a used device bycollection center, provides a final opportunity to interrogate anystored information and/or utilize the receipt itself to function asevidence of prior state changes. Any data collected previously might bestored for download at a collection point. In addition, for situationswhere a return is warranted for replacement or in satisfaction of otherfield action, knowledge of the location of the drug delivery devicethrough distribution and return shipping is valuable. The same signals,in combination with remote authorization of return can allow for returnshipping to be electronically authorized and paid for by the appropriatepartner in the user or distribution network with minimal impact to theuser.

It will be recognized that according to other embodiments of thedisclosure, the various operational states described in regard to FIG. 2may be considered to be optional. For example, it may not be necessaryto make the determinations at blocks 238 and 244 relative to theinsertion of the cannula and the initiation of the administration of thedrug product if, for example, the determinations are made at blocks 232and 250 that the device has been applied and the drug productadministration has been completed. Furthermore, while the method 200includes communication of operational state changes after eachoperational state change, none of the operational state changes may bestored within the system, but the communication of each of theoperational state changes may not occur until block 260. Further, whilethe monitoring of the drug delivery device has been illustrated asoccurring while the method 200 is waiting for certain determinations tobe made (e.g., block 208 and 210), this monitoring need not be performedat every instance illustrated.

Furthermore, it will be recognized that the monitoring described in FIG.2 may include more than monitoring of the various operational statechanges discussed. The monitoring may also include monitoring ofcondition state changes. In fact, the method and system may monitor oneor more sensors to make these operational and/or condition statechanges, which information or signals from the one or more sensors maybe used in the determinations made at various points along the method200.

FIGS. 3A-3C illustrate a method 300 that may be viewed as illustratingsome of the mixed operational and condition state monitoring that mayoccur in a method and system according to the disclosure. The method 300may also be viewed as illustrating how the one or more sensors may beused to determine the state changes described above. Furthermore, themethod 300 may be viewed as providing disclosure of operational andconditions state monitoring and communication of that information notillustrated in FIG. 2.

Referring first to FIG. 3A, the method 300 may begin with the drugdelivery device in the package, and the method waits at block 302 untilit is determined that the package has been opened. At this point, thedevice may optionally be locked until such time as the system conductsone or more validations, verifications or checks to ensure that thedevice is ready to administer, the sterile barrier has been removedand/or the device has been (correctly) applied (see blocks 220, 226, 232of method 220 in FIG. 2). Before conducting each of the one or morevalidations, verifications or checks, the method 300 may determine ifthe drug delivery device is adapted or programmed to carry out thevalidation, verification or check. For example, a determination may bemade at block 304 if the drug delivery device is adapted or programmedto check the sterility of the drug delivery device; in particular, thevalidation or verification may be related to a sterile barrier disposedat the second end of the cannula. If the drug delivery device is adaptedor programmed to perform the sterility check, the method 300 may proceedto block 306, where it is determined if the sterile barrier is disposedover or about the second end of the cannula, for example.

If it is determined at block 306 that the barrier is in place, then themethod may proceed to block 308 where the user is instructed to removethe barrier. The method 300 may then determine at block 310 if thebarrier has been removed. When it is determined that the barrier hasbeen removed, a sterility timer may be started, the expiration of whichmay result in the drug delivery device being placed into or remaining ina locked state, preventing use of the drug delivery device.

If it is determined at block 306 that the barrier is not in place (i.e.,the barrier has been prematurely removed), the method 300 may proceed toblock 312, wherein the delivery device is locked (e.g., a lock orlock-out device is actuated) or the delivery device remains in a lockedstate if the device was previously locked. According to certainembodiments, the locking of the delivery device at block 312 may beirreversible. According to other embodiments, including the embodimentillustrated in FIGS. 3A-3C, the lock may be reversed once it isdetermined that the drug product (e.g., the drug product reservoir) hasbeen replaced at block 314. If the drug product is not replaced, or inthose embodiments where the drug product cannot be replaced (i.e., thelock is irreversible), information regarding the failed sterility checkmay be communicated by the system.

If (i) the determination is made at block 304 that the system is adaptedto validate, verify or check the sterility of the device, (ii) thedetermination is made at block 306 that the barrier is in place and atblock 310 that the barrier subsequently has been removed, or (iii) thedetermination is made at block 306 that the barrier is not in place butthe determination is made at block 314 that the drug product had beenreplaced, the method 300 continues to block 316. At block 316, adetermination is made if the drug delivery device is capable ofperforming visual and/or environmental inspections. If the device is soadapted, the method proceeds to block 318, wherein the determination ismade if the visual inspection and/or environmental conditions are withindesired thresholds. If the determination is made that the visualinspection and/or environmental conditions are outside desiredthresholds, then the method may proceed to blocks 312, 314. If thedetermination is made that the visual inspection and/or environmentalconditions are within desired thresholds, then the method 300 mayproceed to block 320.

At block 320, a determination is made whether the drug delivery systemis able to confirm the user identity. If the drug delivery system is soadapted, then the method 300 continues to block 322, and thedetermination is made if the user identity matches the authorization forthe use of the drug delivery device. If the user is not identified as anauthorized user at block 322, then the method 300 continues to block324, where the drug delivery device is locked or remains locked, andblock 326, where the information regarding the attempted unauthorizeduse is communicated to local and/or remote devices. If the user isidentified as an authorized user, then the method 300 proceeds to FIG.3B and block 328.

At block 328, a further determination is made as to whether the drugdelivery system is enabled to confirm the temperature of the drugproduct. If the system is so adapted, then the method 300 continues toblock 330. At block 330, a determination is made if the drug producttemperature is within a range for predictable delivery (neither too highnor too low). If the determination is made at block 330 that thetemperature is not within the range for predictable delivery, then themethod 300 continues to block 332, wherein a determination is made ifthe device is capable of heating or cooling the drug product to bringthe temperature of the product within the range. If the system is not soadapted, then the method proceeds to block 334, where the device may belocked or remain locked to allow passive heating or cooling to occur andthe user may be alerted. Optionally, the system may also communicate theinformation to local and/or remote devices. If the system is enabled topermit heating or cooling, then the method proceeds to block 336, wherethe device may be locked or remain locked, heating or cooling may beinitiated, and the user may be alerted. Whether passive or activeheating or cooling (blocks 334, 336), the method 300 may continue toblock 338, where delivery is delayed to provide time for the heating orcooling to occur before the method returns to block 330. According tocertain embodiments, the method 300 may terminate after block 330 (incase of excessive temperature, for example) and may communicate thatinformation to local and/or remote devices.

In some embodiments, the temperature check performed at block 330 mayinvolve an evaluation of the temperature history of the drug product todetermine the range and duration of temperatures experienced by the drugproduct in the past (e.g., during storage, distribution, shipping,etc.). If the temperature history of the drug product is unacceptabledue to, for example, the drug product being exposed to elevatedtemperatures for several days or hours during shipping, the controller350 may lockout the drug delivery device 302 so that it cannot be usedto deliver the drug product to a patient, and additionally, may controlthe communication module 352 to transmit a report to the local computingdevice 304 or the remote computing device 306 representative of theunacceptability of drug product's temperature history. In someembodiments, upon a determination that the temperature of the drugproduct exceeds a threshold temperature, the controller may begin atimer that runs until the temperature returns below the thresholdtemperature. If the duration of the timer exceeds a predefined timelimit, the controller 350 may lockout the drug delivery device 302 andcontrol the communication module 352 to transmit a report representativeof the unacceptability of drug product's temperature history.

Returning to FIG. 3B, if the determination is made at block 328 that thedevice is not adapted to perform a temperature check or at block 330that the temperature of the drug product is within the desired range,then the method may continue to block 340, where a determination is madeif the device is enabled to determine that the device is properlypositioned on or oriented relative to the patient. If the device is soadapted, then the method proceeds to block 342, and a determination ismade whether the device is properly disposed or oriented. In thisregard, depending on the preferred insertion site, knowledge of theorientation of the device may be useful in providing a successfulinjection. For example, self-administration into the abdomen would mostlikely result in an orientation of an autoinjector axis approximatelyhorizontal.

If the device is not properly disposed, then the method proceeds toblock 344, and the device may be locked and the user instructed toreposition or reorient the device. The method 300 may then proceed toblock 346 wherein a time delay is provided for the user to repositionthe device before the method 300 returns to block 342 for a furtherdetermination relative to the position of the device. Alternatively, ifthe device is properly disposed, then the method may proceed to block348, and any locks or lockouts that may have been actuated are removed(or the device is unlocked).

The method 300 continues at block 350, wherein a determination is madewhether the system is enabled to determine if the delivery has beentriggered. If the determination is made that the system is so adapted,then the method proceeds to block 352, and a determination is made ifthe device has been activated or triggered. If the determination is madeat block 352 that the device has not been triggered, then the method 300may proceed to block 354 and the system may instruct the user to triggerthe device. According to other embodiments, the drug delivery device maywait for a predetermined and/or preprogrammed time delay to occur beforetriggering the device automatically upon the completion of the timedelay. According to still other embodiments, the method 300 mayoptionally determine if a timer has elapsed at block 355 to reduce therisk of contamination and infection, for example. According to suchembodiments, the timer may be started upon the determination that thebarrier has been properly removed at block 310 (or may be started uponthe determination that the barrier has been removed, according to stillfurther embodiments), and if the method 300 does not determine that thedevice has been triggered within a certain amount of time from thatevent, the method 300 may return to block 312, for example, asillustrated in FIGS. 3B and 3A. If it is determined at block 350 thatthe trigger has occurred, then the method proceeds to block 356, wherethe user may be notified of the triggering of the device and/or thedate, time and location of the delivery may be stored or recorded.Optionally, this information may also be communicated to local and/orremote devices in communication with the system. The method 300 thencontinued to FIG. 3C.

A further determination may be made at block 358 whether the system isenabled to determine if the device has remained properly positioned onor oriented relative to the body. If the system is so adapted, then themethod 300 continues to block 360, and a determination is made if thedevice is properly positioned on or oriented relative to the body. Ifthe device is not properly positioned or oriented, then the method 300may continue to block 362, where the user is alerted to reposition orreorient the device, and block 364, where a time delay is provided forthe user to reposition or reorient the device, before returning to block360 wherein the position or orientation of the device on the patient'sbody is determined. If the device is properly positioned or oriented,the method 300 may proceed to block 366. Optionally, the method 300 mayrepeat block 360 periodically during the time the device isadministering the drug product to ensure that the device remainscorrectly positioned.

At block 366, a determination is made whether the system is enabled todetermine if the administration is complete. If the system is soadapted, then the method 300 continues to block 368, and a determinationis made if the delivery is complete. If the determination is made atblock 368 that the delivery is not complete, then a furtherdetermination is made at block 370 whether the delivery can becompleted. If the delivery is not complete but may be completed, thenthe method 300 returns to block 368 via block 372, where the device ispermitted to continue to administer the drug product. If the delivery isnot complete and cannot be completed (e.g., the device has been removedfrom the patient's skin), then the method 300 continues to block 374,and information regarding the drug and drug delivery may be communicatedto a local and/or remote device. For example, information regardingwhether certain operational states occurred (cannula inserted, deliverystarted, delivery partially completed), the timing of the operationalstates, and the amount of drug product that was administered may becommunicated.

If the determination is made at block 368 that the delivery has beencompleted, then the method proceeds to block 376, where the systemindicates to the user that the delivery is complete. Furthermore, themethod 300 communicates information regarding the drug delivery, thedrug delivery device, and the drug product to local and/or remotedevices at block 378. For example, the information may include thatcertain operational states occurred and the timing of the operationalstates. The method 300 may also verify that the device was correctlypositioned throughout, where the system is enabled to make thisdetermination. The method 300 may also pass to block 378 if the systemis not enabled to determine if the administration of the drug product iscomplete, the assumption made that the drug delivery device having beendetermined to have passed through one or more of the precedingoperational states necessarily leads to the conclusion that the deliverywas completed.

Again, it should be noted that while the above description relates to amethod including a series of states of for the devices and alternativeactions that may depend on those states, the device need not determineeach and every state or perform each and every action illustrated inFIGS. 3A-3C. Rather, it will be recognized that one of ordinary skill inthe art may omit or eliminate the determination of certain states orperformance of certain actions, so as to result in a system that maycontrol the device based on or communicate a subset of the statesdescribed.

Having discussed the possible methods of operating the drug deliverysystem in the context of the illustrated methods of FIGS. 2 and 3A-3C,the possible methods of operating one or more computing devices incommunication with the drug delivery system is now discussed in thecontext of a method 400 illustrated in FIG. 4. It will be recognizedthat the method 400 may be carried out by a single computing device,such as the server 104 illustrated in FIG. 1. Alternatively, the actionsdiscussed with respect to FIG. 4 may be carried out by multiplecomputing devices, such as the mobile device 110 or computing device 114in conjunction with the server 104.

The method 400 begins at block 402 with a determination as to whether areport has been received from the drug delivery system. If no report hasbeen received, the method 400 waits at block 402 Once it is determinedthat a report has been received at block 402, the method 400 proceeds toblock 404.

At block 404, the report received from the drug delivery system is usedto update one or more records. In this regard, the one or more computingdevices adapted or programmed to carry out the method 400 may performthe actions of retrieving the one or more records from storage in one ormore memory storage devices, writing the information received from thedrug delivery device into the one or more records, and then storing theone or more records in the one or more memory storage devices. The oneor more memory storage devices may be part of the one or more computingdevices, may be separate from the one or more computing devices, or mayinclude one or more of the memory storage devices that are part of theone or more computing devices and one or more memory storage devicesthat are separate from the one or more computing devices (i.e., therecord is stored at the computing device and in backup storage separateand possibly remote from the computing device).

As mentioned above, the report may be used to update one or morerecords. For example, there may be one record for the individual patientthat is stored in a patient record database. The patient record may beused, for example, to track the compliance of the individual patient(e.g., patient 102) with his or her regime(s). There may also be arecord for the drug delivery system used by the individual patient thatis stored in a drug delivery system database. The drug delivery systemrecord may be used to store information regarding the drug deliverysystem throughout the life of the drug delivery system. The drugdelivery system record may be accessed by the drug delivery systemmanufacturer or the drug provider for quality control purposes (e.g., tomonitor individual instances of the drug delivery system for faults orfailures attributable for to the drug delivery system, or to track theenvironmental condition histories of one or more drug delivery systemsfor patterns that may assist in determining improvements in the design,packaging, shipment or handling of the drug delivery systems). There mayalso be record for drug used in the drug delivery system that is storedin a drug database. This record may be used in a similar fashion to thedrug delivery system record for quality control purposes.

In addition to the updating the records at block 404, the computingdevice adapted or programmed to carry out the method 400 may be adaptedor programmed to carry out one or more actions based on the informationin the report received from the drug delivery system. For example, thecomputing device may be adapted or programmed to carry out an action atblock 406. This action may require not only the information received inthe report and/or stored previously in the record updated at block 404,but may require additional information such as from other patientrecords, drug system delivery records and/or drug records. If this isthe case, the determination may be made at block 408 that these otherrecords need to be accessed, and the information retrieved at block 410(e.g., by retrieving these other records from the patient, drug deliverysystem and drug databases and reading the information from these recordsonce retrieved). The action may then be carried out at block 412.

As one example, the one or more computing devices adapted or programmedto carry out the method 400 may be adapted or programmed to use theinformation received in the report to prepare a compliance history forthe patient, which compliance history tracks uses of instances of thedrug delivery system by the individual patient relative to his or hertreatment regime to determine how successful the patient has been infollowing the treatment regime and which compliance history may bestored in the patient record. In addition, the one or more computingdevices may determine if a pharmacy should be contacted to orderdelivery of additional drug delivery devices for the individual patient,and may generate a communication to be sent to the pharmacy to order thedelivery of additional drug delivery systems. Further, the one or morecomputing devices may determine if a reminder should be sent to thepatient, via the mobile device 110 for example, to improve or supportcompliance with the individual patient's treatment regime, in which casethe one or more computing devices may generate a communication to besent to the patient or user of the device. Further, the one or morecomputing devices may determine that the operation of the drug deliverydevice should be modified because of a conditional state received fromthe drug delivery device, for example. For example, the one or morecomputing devices may determine that the drug delivery system should belocked to prevent its use because of the temperature history of the drugin the drug delivery system, for example. In this case, the one or morecomputing devices may generate a communication, in the form of a signalfor example, to be sent to the drug delivery system to lock the drugdelivery device that is part of the drug delivery system. Other possibleactions are discussed in detail below, although this discussion is forillustrative purposes only and is not intended to be limiting.

Depending on the action taken at block 412, or even if it is determinedat block 406 that no action need be taken, the method 400 may proceed toblocks 414, 416, 418 where determinations are made if the computingdevice should make contact with other parties (block 414), interact withthe patient (or user, if not the same as the patient) (block 416) orcontrol the drug delivery device that is part of the drug deliverysystem (block 418). For example, as discussed above, the action taken atblock 412 may involve the generation of communications or signals to besent to third parties, such as the pharmacy, to the patient, or to thedrug delivery device. In such a case, the one or more computing devicesmay carry out the actions of block 420, 422, 424 as dictated by thedeterminations made at blocks 414, 416, 418. Alternatively, the one ormore computing devices may carry out the actions of blocks 420, 422, 424even if it is determined that no action need be taken at block 406. Forexample, the one or more computing devices may forward certaininformation to third parties 420 based solely on the receipt of theinformation in a report from the drug delivery device, such that thereis no need to separately determine that an action need be taken inregard to the information received (i.e., the communication isautomatically sent based on the fact that the information has beenreceived, with the one or more computing devices acting as a repeaterstation for such information). The receipt of information from the drugdelivery device may also prompt communications to be sent to thepatient/user or control signals to be sent to the drug delivery systemwithout a separate determination that such action need be taken, thecommunication or control signal being sent simply because certaininformation and/or reports were received from the drug delivery system.

Having made the determinations at blocks 414, 416, 418 and carried outthe actions of blocks 420, 422, 424, the method 400 may return to block402 to await the next report. It will be recognized that the one or morecomputing devices may perform the actions of the method 400 in parallelfor each of the reports received from different instances of the drugdelivery system, or may perform this steps in sequence for each report.If performed in parallel, the one or more computing devices maydetermine if action is to be taken in regard to one report, while theone or more computing devices may be interacting with another patient inregard to the information contained in the report received from thatpatient. Furthermore, the one or more computing devices carrying out themethod 400 need not be adapted or programmed to carry out each of theactions described above according to every embodiment of the one or morecomputing devices. For example, one of the one or more computing devicesmay be adapted or programmed to update records for each patient and todetermine if an interaction with that patient is required, while anotherof the one or more computing devices may be adapted or programmed toupdate records for each drug delivery device and to determine is acontrol signal should be sent to the drug delivery device, while anotherone of the one or more computing devices does not update any record, butis adapted or programmed to access, for example, a patient record anddetermine if the pharmacy needs to be contacted to order additionalinstances of the drug delivery system for the patient associated withthe patient record accessed and to generate the communication if theorder of additional instances of the system is required.

It will be appreciated that the methods 200, 300, and 400, above, touchonly a fraction of the possible state and identity information that maybe used to control and/or monitor the drug delivery device and that maybe communicated between the drug delivery system and the one or morecomputing devices, as well as how that information is used by the drugdelivery system and the one or more computing devices. Additionalembodiments are possible according to the disclosure.

For example, a non-limiting matrix of state and identity information mayinclude the following:

Condition State Information:

-   -   Temperature    -   Shock or vibration exposure    -   Light exposure    -   Color and/or turbidity (as relates to the drug)    -   Orientation    -   Geographic position    -   Temporal information

Operational State Information:

-   -   Device removed from package    -   Device removed from cold storage (e.g., refrigerator)    -   Device/drug temperature ready for administration    -   Delivery triggered    -   Device applied to patient    -   Device applied at correct location/orientation on patient    -   Cannula inserted into patient and/or inserted into correct        tissue    -   Delivery in progress    -   Delivery complete    -   Error has occurred

Device Identity Information:

-   -   Drug name or identification, concentration, and/or amount    -   Security and/or anti-counterfeiting information    -   Patient prescription/therapeutic regime

Patient Identity Information:

-   -   Point of Care diagnostics on patient    -   Self-analyzed measure of progress    -   Fingerprint, pin, or other secure identification information

This information may be used to control the drug delivery system ordevice, to be communicated to other computing devices, or otherwise tobe used, and an exemplary listing of certain additional uses is includedbelow. The listing and additional comments below is not intended tosupersede, but to augment the discussion above, and is intended to benon-limiting.

As one example, the drug delivery system or the one or more computingdevices may make a determination regarding the authenticity of the drugand its compliance with manufacturing standards. Such a determinationmay be made by the drug delivery device at block 220 of method 200 orblock 318 of method 300, or by the one or more computing devices atblock 406 of method 400, for example. The determination may be madebased on the temperature, shock or vibration exposure, and/or lightexposure of the drug delivery device/drug (or a history of one or moreof these conditions) and color and/or turbidity of the drug (asdetermined by an optical inspection). This determination may result incontrol of the drug delivery device to either lock or unlock the device,according to the determination made. See blocks 220, 222, 224 of method220, blocks 318, 312, 314 of method 300, and blocks 406-412 and 418, 424of method 400.

As another example, the drug delivery system or the one or morecomputing devices may make a determination whether the drug isappropriate for the patient. See block 220 of method 200, block 322 ofmethod 300, and block 406-412 of method 400. The determination may bemade based on one or more of the items of device of patient identityinformation listed above, and may also result in control of the drugdelivery device to either lock or unlock the device, according to thedetermination made. See blocks 220, 222, 224 of method 220, blocks 322,324, 326 of method 300, and blocks 406-412 and 418, 424 of method 400.

As a further example, the drug delivery system or the one or morecomputing devices may make a determination whether the dose has beencorrectly administered. This determination may be carried out afterdetermining that the drug is appropriate for the patient and/or that thedrug is authentic (e.g., not counterfeit) and is in compliance withmanufacturing standards. See the preceding paragraphs. The determinationwhether the dose has been correctly administered may depend on one ormore of the types of operational state information listed above. Seeblocks 220-260 of method 200, and blocks 328-378 of method 300. Thisinformation may be used to update the patient record, determine thepatient compliance or therapy progress, and may prompt communicationwith the pharmacy regarding a refill, or with the payer (e.g., insurancecompany) to authorize payment for the drug delivery device. See blocks404-414 of method 400, and servers 142, 144 of FIG. 1.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determinationregarding the operational state of the drug delivery device, and togenerate instructional messages to guide the user through the actionsrequired for the proper use of the drug delivery device. Thedetermination may be based on any of the operational state informationlisted above, and the instructions generated may be dictated by theactions that need to be performed after the operational state that hasjust occurred. Implementation of interactive instructions that followthe changing states of the drug delivery device may help the user haveconfidence in administration of the drug. See also, FIGS. 6 and 7,below.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatother people nearby are taking the same medication. See blocks 406-412of method 400. This determination may be made based on the drug identityinformation and the patient identity information, in combination withthe drug delivery system geographic location information. Thisdetermination may prompt a communication with the patient (see blocks416, 422 of method 400) regarding local support networks of persons withsimilar conditions and/or taking similar drugs or medication to permitthe patient to receive support and encouragement from such networks.Alternatively, the determination may prompt a communication with thelocal support network(s) (see blocks 414, 420 of method 400) to providesupport and encouragement to the patient. As a further alternative, thedetermination may prompt a personalized intervention communication to besent to the patient (again, see blocks 416, 422 of method 400).

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determinationwhether the patient is not in compliance with their therapy regime. Seeblocks 406-412 of method 400. The determination may be based in part onthe drug identification information, such as the prescribed treatmentregime, in part on condition state information, such as the passage oftime, and in part on the operational state information, such as wherethe drug delivery device is removed from the packaging but where noadditional operational state information is determined, reported orreceived during the passage of time from the removal from packagingoperational state. Based on this information, the drug delivery systemand/or the one or more computing devices may determine that aninteraction with the patient should be generated, such as an alert maybe displayed or sent to patient. See blocks 416, 422 of method 400.Furthermore, the drug delivery system and/or one or more computingdevices may determine that a communication should be generated to bedisplayed or sent to a healthcare provider, caregiver, support giverand/or payer to encourage adherence to regime. See blocks 414, 420 ofmethod 400.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatthe patient needs more medication (a refill). See blocks 406-412 ofmethod 400. The determination may be based in part on the drug identityinformation, such as the prescribed treatment regime, and in part on theoperational state information, such as where the drug delivery has beencompleted. Based on this information, the one or more computing devicesmay generate a communication that is sent to the payer and/or pharmacyto request a prescription refill. See blocks 414, 420 of method 400.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatthe injection was not performed correctly. See blocks 406-412 of method400. The determination may be based in part on operational stateinformation, in comparison with information that may be collected andstored regarding conventional norms in operation. Alternatively oradditionally, a comparison between the determined, reported or receivedoperational states may permit a determination to be made that theinjection was not performed correctly. For example, the determination,reporting or receipt of operational state information indicating thatthe drug delivery is complete without operation state informationindicating that device was triggered, that the device was applied to thepatient, and/or that the cannula was inserted may indicate that the drugdelivery device has failed to perform correctly, is faulty or wasoperated incorrectly.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatpatient's condition is improving. The determination may be based in parton patient identity information, such as point-of-care diagnosticsperformed on the patient (e.g., blood glucose test or other testing) orself-analysis reporting, and in part on the determination, reporting orreceipt of operational state information, such as where the drugdelivery has been completed. The determination may rely upon an overalltrend as opposed to individual determinations or reports, as it isbelieved that data or reporting trends are usually more indicative ofimprovement in a patient's condition than the patient's condition asdetermined at individual instances for serious diseases. As such, theinformation gathered regarding the patient and the operational state ofthe drug delivery system/device may be combined with combined withtherapy compliance history. This determination may result inindividualized interventions to be generated, which interventions (suchas encouraging messages and other forms of positive reinforcement) mayincrease persistence in therapy.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination of thetime of day (or week, month, etc.) that the patient usually takes theirmedication. This determination may be based, in part, on the patientrecord in which time information is associated with operational stateinformation, such as relates to the triggering of the drug deliverydevice or the completion of the drug delivery. This determination mayalso rely on device identity information, such as the prescribedtreatment regime. Based on this determination, the one or more computingdevices may generate a reminder communication that is sent, for example,to the mobile device 110 to alert the patient that the time isapproaching for them to administer their next dose. As the usefulness ofreminders is enhanced when there is reasonable access to the drugdelivery device and an opportunity for its use, it is beneficial toreinforce a patients decision to take their medication at a particulartime during the day, week, month, etc. Based on this determination, theone or more computing devices may also generate a personalizedintervention, such as a message of encouragement to be used as apositive reinforcement.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination wherethe patient usually takes their medication. This determination may bebased, in part, on the patient record in which geographic positioninformation is associated with operational state information, such asrelates to the triggering of the drug delivery device or the completionof the drug delivery. This determination may also rely on deviceidentity information, such as the prescribed treatment regime. Based onthis determination, the one or more computing devices may generate areminder communication that is sent, for example, to the mobile device110 to alert the patient that the time is approaching for them toadminister their next dose when they are at or near the geographiclocation where the patient usually uses the drug delivery system. As theusefulness of reminders is enhanced when there is reasonable access tothe drug delivery device and an opportunity for its use, it isbeneficial to reinforce a patient's decision to take their medicationwhen they are in the usual location where they take their medication.Based on this determination, the one or more computing devices may alsogenerate a personalized intervention, such as a message of encouragementto be used as a positive reinforcement.

Of course, the determinations regarding the usual time and location ofthe use of the drug delivery device may be combined, and the one or morecomputing devices may generate a message only when the patient or useris at or near their usual location of use at or near the time theyusually use the drug delivery device.

While the foregoing has focused principally on the determinations madeby the drug delivery system and/or one or more computing devicesconcerning the patient or the patient's use of the drug delivery device,determinations may be made with reference to the drug delivery device orthe drug before the drug delivery device is made available to thepatient or user.

For example, the drug delivery system or the one or more computingdevices may use the information to make a determination whether deliveryof a certain number of doses of a particular drug has arrived (e.g.,instances of a drug delivery device containing the particular drug), forexample, at a particular distributor or pharmacy location. Thisdetermination may be made based in part on the geographic locationinformation and in part on the drug identity information. Based on thisinformation, the one or more computing devices may generate acommunication that is sent to the pharmacy or distributor (via thepharmacy or distributor server, for example) to inform them of thedelivery of the drug delivery device. The pharmacy or distributor mayuse such a smart drug delivery device to simplify their logistics andinventory systems, for example.

Along similar lines, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatone or more of the drug delivery devices have been damaged en route to aparticular distributor or pharmacy location. The determination may bemade based in part on the geographic location information and in part onthe drug identity information. The determination may also be based inpart on condition state information, such as the temperature,shock/vibration exposure, light exposure or color and/or turbidity ofthe drug, whether determined at a particular time or over a period oftime (i.e., a history as established in the drug delivery device recordor the drug record). The determination may also or instead be based inpart on the age of the product relative to its manufacture date orexpiration date. The determination may also or instead be based in parton operational state information, such as the removal of a sterilitybarrier from the second end of the cannula of the drug delivery device.Based on this information, the one or more computing devices maygenerate a communication that is sent to the pharmacy or distributor(via the pharmacy or distributor server, for example) to inform themthat the drug delivery device has been damaged or expired. The pharmacyor distributor may use such a smart drug delivery device to expedite thedistributor's or the pharmacy's replacement of the damaged or expiredproduct and prevent delays in patient therapy, for example.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatthe product is as stated and has not been counterfeited. Such adetermination may be based on the drug identity information, such as thename, concentration and amount of the product and the security andanti-counterfeiting measures associated with the drug. The determinationmade by the one or more computing devices may cause a communication tobe generated, which communication may be transmitted to a governmentalagency (e.g., customs/immigration officials) via the governmental agencyserver, to distributors and/or pharmacies via their respective servers,and/or patients and caregivers via their personal mobile devices.

As still further alternatives, certain determinations made by drugdelivery systems and/or one or more computing devices operatingaccording to embodiments of the disclosure may be used to control thedrug delivery device remotely (i.e., without the controlling devicebeing present in the same geographic location (e.g., room, building, orcity) as the drug delivery device).

For example, the drug delivery system or the one or more computingdevices may use the information to make a determination that the deviceneeds to be controlled to prevent accidental operation. Thedetermination may be based in part on the drug identity information incombination with, for example, certain patient identity information,such as biometric information in the form of a fingerprint. If it isdetermined that a party that is not authorized to use the drug deliverydevice is attempting to use the drug delivery device, then the one ormore computing devices may generate a signal to be sent to the drugdelivery system to lock the drug delivery device or to keep it lockeduntil the drug delivery system is accessed by the patient or user forwhich it is intended.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatthe patient associated with the drug delivery device is in a particulargroup or subgroup of patients or users that require or prefer aparticular mode of operation for the drug delivery device. Thisdetermination may be made in part using information regarding theidentity of the patient and the drug. Based on this determination, thedrug delivery system and/or the one or more computing devices maygenerate a signal that customizes the operation of the drug deliverydevice. For example, the drug delivery device may be customized as tothe sounds and/or lights used to alert the patient to various conditionor operational states according to the specific market segment orpatient population associated with the patient. As one example,different sounds may be used with pediatric patients than adultpatients, louder sounds may be used with patients with hearing loss, anddifferent lights or light sequences may be used with color-blindpatients. Such control of the drug delivery device through the drugdelivery system and/or one or more computing devices may reduce costsfor drug delivery by permitting a single drug delivery device to be usedthat adapts to patient via software, rather than to use a plurality ofdifferent drug delivery device types, each of which has differenthardware from the other types of drug delivery devices.

As a further alternative, the drug delivery system or the one or morecomputing devices may use the information to make a determination thatthe drug delivery device has not performed properly, and to generate acommunication in that regard to the manufacture of the drug deliverydevice. The manufacturer may then determine modifications and/orimprovements to enable proper administration of drug and can implementchecks for sensed information and relay errors if it is not followed oris not successful.

As has been mentioned above, the drug delivery system and/or one or morecomputing devices in communication with the drug delivery system neednot be adapted or programmed to carry out every action listed in FIGS.2, 3A-C and 4. Several illustrations of embodiments of a drug deliverysystem or computing device according to the disclosure are now discussedrelative to FIGS. 5-12B. FIGS. 5-12B illustrate methods for operatingthe drug delivery system or the computing device that represent a subsetof the actions discussed above in regard to FIGS. 2, 3A-C and 4 andassociated systems. FIGS. 5-9 relate to a method concerning a sterilitybarrier, while FIG. 10 relates to activation of the device, and FIGS. 11and 12A-12B relate to the needle shield.

Turning first to FIG. 5, a method 500 is illustrated wherein the drugdelivery system is adapted or programmed to provide instruction to thepatient or user, through the use of an output devices such as a lightemitting diode, display, speaker or other device, and to communicatewith a computing device (e.g., mobile device 110 or computing device114) over a communication link (e.g., 112 or 116) to transmit a reportto that computing device. The method 500 is focused on a single issue:whether the sterility of the device is intact. The method 500 determinesif the sterility of the device is maintained based on whether a barrier,in the form of a needle cap, is disposed over the second end of acannula that is intended to be inserted into the patient.

The method 500 begins by making a determination whether the needle capis in place at block 502. This determination may be made, at least inpart, on whether a signal has been received by a controller adapted orprogrammed to carry out the method 500 from a switch or other proximitysensor that abuts a structure of an autoinjector when the needle cap isproperly disposed over the end of the needle. If the determination ismade at block 502 that the needle cap is in place, then the method 500continues to block 504 and the user may be instructed to remove theneedle cap, for example by illuminating one or more light emittingdiodes visible to the patient or user of the drug delivery device. Thecontroller may also cause a transmitter (which is at least capable ofone-way communication, and may be capable of two-way communication—i.e.,a transceiver) to transmit a report at block 504 to one or morecomputing devices in communication with the transmitter representativeof the fact that the sterility of the device is intact. For example, thetransmitter may be a near field transmitter, such as may use theBluetooth or similar protocol.

The method 500 may continue at block 506, where the controllerdetermines if the needle cap has been removed after the patient or userwas instructed to remove the needle cap. For example, the controller maydetermine that the needle cap has been removed when a different signal(or no signal) is received from the switch or other proximity sensor.When the controller determines that the needle cap has been removed, themethod continues to block 508 where the controller causes thetransmitter to transmit a report representative of the fact that theneedle cap has been removed after the sterility of the device wasconfirmed.

As illustrated in FIG. 5, the method 500 includes a different set ofactions if the controller determines at block 502 that the barrier isnot in place, e.g., the needle cap is not disposed about the end of theneedle at the beginning of the process. If such a determination is madeat block 502, then the method 500 continues at block 510, where thecontroller locks the drug delivery device, instructs the patient or userto replace the product container, and causes the transmitter to transmita report representative of the fact that the sterility of the device isnot intact. As was the case with the action taken at block 504, thecontroller may instruct the patient or user to replace the product byilluminating a light emitting diode. The controller may lock the productby preventing the operation of one or more other assemblies necessary toadminister the drug to the patient; for example, the controller mayprevent the needle from being inserted into the patient. The controllerthen waits until a determination is made at block 512 that the producthas been replaced. The controller may determine that the product hasbeen replaced depending on whether a switch proximate to the containerhas changed states, which the switch would do only if the container wasreplaced. When the controller determines that the product has beenreplaced, the method 500 continues to block 514, and the controllercauses the transmitter to transmit a report to one or more computingdevices in communication with the drug delivery system representative ofthe fact that while the sterility of the device was not initiallyintact, the product has been replaced.

By contrast to the method 500 of FIG. 5 which is carried out by a drugdelivery system with a controller adapted or programmed to carry out themethod 500, the methods 520, 540 of FIGS. 6 and 7 are carried out by adrug delivery system and an associated computing device, which drugdelivery system is adapted or programmed to carry out the method 520 andwhich computing device is adapted or programmed to carry out the method540. It will be recognized that the methods 520, 540 may limit theamount of hardware required by the drug delivery system by shiftinginteractive events with the patient or user to the computing device,which may be in the form of a mobile device 110, to take advantage ofthe output devices or peripherals already associated with the computingdevice.

The method 520 of FIG. 6 begins at block 522, with a controller that ispart of the drug delivery system determining if the barrier is intact,i.e., the needle cap is disposed over the end of the needle. If thedetermination is made that the needle cap is initially in place, thecontroller causes a transmitter to transmit a report to the computingdevice representative of the fact that the needle cap is disposed overthe end of the needle at block 524.

The method 540 of FIG. 7 begins with receipt of the report from the drugdelivery device at block 542. If the computing device determines that areport has been received and that the report received is representativeof the fact that the needle cap is initially in place, the method 540proceeds to block 544, wherein the computing device controls anassociated display to display a message to the user or patient that theneedle cap should be removed. According to one embodiment of thedisclosure, where the computing device is a hand-held mobile device,such as a smart phone, the message may be displayed on the displayassociated with the mobile device in the form of an image that mayinclude words, pictures or a combination thereof representative of theinstruction to remove the needle cap. The method 540 then passes toblock 546, where the computing device waits to receive a report from thedrug delivery system representative of the fact that the needle cap hasbeen removed.

Returning to FIG. 6, the method 520 continues at block 526 where thecontroller associated with the drug delivery device determines whetherthe needle cap has been removed after the initial determination was madethat the needle cap had not been removed initially. The controllerbegins this determination upon completion the transmission of the reportat block 524, and thus the determination is not dependent upon thepatient or user receiving the instruction via the computing device toremove the needle cap, although according to certain embodiments thedetermination of the controller whether the needle cap has been removedat block 526 could be made dependent upon the user first receiving amessage from the computing device that the needle cap should be removed.When the controller determines that the needle cap has been removed, themethod 520 continues at block 528, where a report is transmitted to thecomputing device representative of the fact that the needle cap has beenremoved.

Returning to FIG. 7, upon determination at block 546 that a report hasbeen received by the computing device that the needle cap has beenremoved, the method 540 may continue at block 548 where a report istransmitted, for example by the mobile device 110 in FIG. 1 to theserver 104 in FIG. 1 via the network 118, representative of the factthat the drug delivery system is ready for use. According to otherembodiments the report may be more particular, e.g., representative ofthe fact that the barrier was initially intact and that the needle caphad been subsequently removed.

In the alternative, the controller of the drug delivery system maydetermine at block 522 that the barrier is not initially in place. Ifso, the controller may lock the drug delivery device and cause thetransmitter to transmit a report to the computing device representativeof the fact that the barrier was not initially in place at block 530.The controller of the drug delivery system may then determine at block532 if the product has been replaced.

Meanwhile, the computing device has received the report representativeof the fact that the barrier is not initially in place at block 542, andthe method 540 has continued to block 550, where the device controls anassociated display to display a message to the user or patient that theproduct should be replaced. According to the embodiment of thedisclosure discussed above, where the computing device is a hand-heldmobile device, the message may be displayed on the display associatedwith the mobile device in the form of an image that may include words,pictures or a combination thereof representative of the instruction toreplace the product. The method 540 then continues at block 552, wherethe computing device determines if a report has been received from thedrug delivery system representative of the fact that the drug producthas been replaced.

Shifting again to FIG. 6, once the determination is made at block 532that the product has been replaced, the controller may cause thetransmitter to transmit at block 534 a report representative of the factthat the product has been replaced. When the computing device determinesthat the report has been received at block 552 in FIG. 7, the method 540continues to block 548, where a report is transmitted to the server 104,for example, representative of the fact that the drug delivery device isready for use.

It is not a requirement of the disclosure that the determinationsregarding condition state information, operational state information orother information be made by a controller that is housed in the samehousing as the drug delivery device, or the computing device for thatmatter. In fact, the controller that makes the determination regarding aparticular state of the drug delivery device may be disposed in ahousing that is detachable from the drug delivery device. For example,again with reference to an embodiment that determines if a sterilitybarrier is intact based on whether a needle cap is disposed over the endof a needle, a method 560 is provided in FIG. 8 for a controller that isdisposed in the needle cap and that is coupled to a sensor, such as aswitch or other proximity sensor, that will determine when the needlecap is removed from the end of the needle.

Before discussing the method 500, it may be helpful to discuss theillustration of FIG. 9, which includes the needle cap 600 and portionsof an embodiment of an autoinjector 602 with which the needle cap 600 isused. It will be recognized that much of the construction of theautoinjector 602 has been omitted to facilitate discussion of thestructure and operation of the needle cap 600. The autoinjector 602 mayinclude other structures, subassemblies, and/or assemblies that may, forexample, insert a cannula into a patient and force a drug or medicamentfrom a reservoir through the cannula into the patient. In this regard,reference is made to the embodiment of an autoinjector illustrated inFIG. 13, below.

According to the simplified presentation of the autoinjector 602illustrated in FIG. 9, the autoinjector includes a reservoir 604 in theshape of a syringe. Thus, the reservoir 604 is defined by asubstantially cylindrical wall 606 having a hub 608 in which a cannula610 is disposed and fixed (or staked). The cannula 610 has a first end612 in fluid communication with an interior 614 of the reservoir 604,and a second end 616 that is intended to be inserted into the patient.The reservoir 604 may also include a plunger 618 that moves along thereservoir 604 to force fluid out of the reservoir 604 through thecannula 610 into the patient. The autoinjector 602 also includes astructure 620 that cooperates with structures of the needle cap 600,which structure 620 is disposed about the cannula 610. The structure 620may be, for example, a needle shield (explained in greater detailrelative to the embodiment of FIG. 13), or a portion of a housing of theautoinjector 602.

The needle cap 600 includes an annular collar (or hub) 622 in which thehub 608 of the reservoir 604 is received. The collar 622 fits snuglyabout the hub 608 at one end and receives the second end 616 of thecannula 610 in an interior space 624 of the collar 622. The collar 622may also be described as disposed about the second end 616 of thecannula 610. The collar 622 is attached to a body 626 (that may be inthe form of a housing) in which is disposed a power supply 628 and acontroller/communication module assembly 630. The power supply 628 andthe module assembly 630 may be coupled through the use of a switch 632,which as illustrated includes first and second contacts 634, 636. Whenthe contacts 634, 636 abut each other, the module assembly 630 iscoupled to the power supply 6268.

In particular, as is illustrated in FIG. 9, the first contact 634 abutsthe needle shield 620 with the needle cap 600 disposed about the secondend 616 of the cannula 610, and thus does not abut an end 638 of thesecond contact 636 in this first state. When the needle cap 600 isremoved (second state), the first contact 634 is free to move in thedirection of the second contact 636 and to abut the end 638 of thesecond contact 636. With the contacts 634, 636 abutting each other, thecircuit is closed and the module 630 is coupled to the power supply 628.

According to the method 560 of FIG. 8, the controller of the module 630may determine based on a signal received (or not received) from theswitch or sensor 632 that the needle cap 602 is disposed over the end616 of the needle 610 at block 562. The sensor may be extremely simplein regard to this embodiment, and may even include a pair of contacts634, 636 that are ordinarily disposed on opposite sides of the needleshield or housing 620 or are otherwise spaced apart by the needle shieldor housing (see FIG. 9), but that are connected or coupled when theneedle cap 602 is removed (such that the needle shield or housing 620 isno longer disposed between the contacts 634, 636 or no longer preventstheir contact with each other). In fact, according to such anembodiment, the sensor 632 and the controller of the module assembly 630may be the same structure. When the module 630 determines that theneedle cap 602 has been removed, the module assembly 630 controls theassociated transmitter to transmit a report representative of the factthe needle cap 602 has been removed at block 564. Again, according tothe embodiment where the contacts 634, 636 are the sensor 632, theconnection or coupling of the contacts 634, 636 may close a circuitincluding the transmitter 630 and a power supply 628 (e.g., a battery),which causes the transmitter 630 to transmit the required report.

FIGS. 10 and 11 illustrate methods similar to that of FIG. 8, in thateach method is focused on the determination of a single condition oroperational state of the drug delivery device, and transmits a reportwhen the condition or operational state occurs. In this regard, themethod 570 focuses on determining if the drug delivery device has beentriggered by determining if an actuator (e.g., a button) has beendepressed, and the method 580 focuses on determining if a needle shieldthat is part of the drug delivery device has deployed (which needleshield deployment ordinarily occurs after the drug delivery has beencompleted and the drug delivery device is removed from against the skinof the patient). As was also the case with the embodiment of FIG. 9, theembodiments of FIGS. 10 and 11 may be carried out through the use of asensor in the form of a switch or pair of contacts that closes a circuitincluding the transmitter and a power supply upon determination of theoperational state.

Thus, according to FIG. 10, the method 570 begins at block 572, wherethe controller/switch determines if the actuator has been depressedaccording to whether the switch state has changed in accordance with theswitch contacting a portion of the drug delivery device that would notordinarily be in contact with the switch unless the button was depressed(see, e.g., switch 766 in FIG. 13). For example, the switch may beattached to and carried on the actuator (e.g., button), such that whenthe actuator moves relative to the housing of the drug delivery device,the switch comes in contact with a structure of the drug delivery devicethat changes its state. When this occurs, the method 570 continues atblock 574, and the controller/switch causes the transmitter to transmita report representative of the fact that the drug delivery device hasbeen trigger by closing a circuit between the transmitter and a powersupply (e.g., a battery, capacitor or inductive power supply). Thetriggering of the drug delivery device may coincide with the activationof a drive associated with a reservoir to cause a medicament to beejected from the reservoir, although the activation of the drive neednot coincide with the triggering of the drug delivery device.

In a similar fashion, according to FIG. 11, the method 580 begins atblock 582, where the controller/contact pair determines if the needleshield 656 has been deployed according to whether the contact pair hasbeen connected or coupled together. As illustrated in FIGS. 12A and 12B,an embodiment of a drug delivery device system for carrying out themethod 580 may include a reservoir 650 in the form of a syringe, havinga cannula 652 in the form of a needle with an end 654 that is to beinserted into the patient (see FIG. 12A) and a needle shield 656 thatincludes a conductive pad 658 that connects the contact pair 660, 662when the needle shield 656 is deployed in distal position;alternatively, one of the contact pair 660, 662 may be disposed on thehousing of the drug delivery device and the other of the contact pair660, 662 may be disposed on the needle shield 656, such that when theneedle shield 656 moves relative to the housing of the drug deliverydevice, the contacts 660, 662 are connected or coupled. Moreparticularly, after the needle shield 656 has moved in the distaldirection from a proximal position (where the needle shield 656 does notsurround the distal end 654 of the delivery cannula 652) to a distalposition (where the needle shield 656 surrounds the distal end 654 ofthe delivery cannula 652), the conductive pad 658 may contact each oneof the contact pair 660, 662, thereby forming a closed electricalcircuit. When this occurs, the method 580 continues at block 584, acircuit including a power supply 664 and a controller and transmittermodule assembly 668 is closed, causing the transmitter of the module 668to transmit a report representative of the fact (under mostcircumstances) that the drug delivery has been completed. Accordingly,the report representative of the completion of drug delivery istransmitted in response to the needle shield 656 being disposed aboutthe distal end 654 of the delivery cannula 652 after having been movedfrom its proximal position to its distal position.

In some embodiments, the contact pair 660, 662 may be part of a latchingcircuit. The latching circuit may be configured such that, initially,contact between the conductive pad 658 and the contact pair 660, 662powers the transmitter module assembly 668. Subsequently, after a periodof time, the latching circuit powers the transmitter module assembly 668independently of the contact between the conductive pad 658 and thecontact pair 660, 662. Thus, the latching circuit helps ensure that thetransmitter module assembly 668 is supplied with power even if theconductive pad 658 is inadvertently moved out of contact with thecontact pair 660, 662 after its initial contact with the contact pair660, 662.

According to one alternative embodiment, using the structure of FIGS.12A and 12B, a repositioning of the contacts 660, 662 relative to theconductive pad 658 would permit the system of FIGS. 12A and 12B todetermine if the needle shield 656 has been moved relative to the end654 of the cannula 652 so as to determine that the cannula 652 has beeninserted into the patient. Rather than movement of the needle shield 656toward the bottom of the page causing the conductive pad 658 to closethe circuit between the contacts 660, 662, movement of the needle shield656 toward the top of the page would cause the conductive pad 658 toclose the circuit between the contacts 660, 662, which would cause themodule assembly 668 to transmit a report representative of the fact thatthe needle has been inserted. As a further alternative embodiment, twosets of contacts may be included, the sets spaced from each other in thedirection of movement of the needle shield 656, with the set of contactsclosest to the top of the page being used to determine if the needleshield 656 has been moved relative to the end 654 of the cannula 652indicative of insertion of the end 654 into the patient, and the set ofcontacts closest to the bottom of the page being used to determine ifthe needle shield is disposed about the end 654 of the cannula 652indicative of the completion of the delivery to the patient.

The methods discussed above may be carried out by a variety of differentdrug delivery systems. FIGS. 13 and 14-16 illustrate two examples ofsuch systems, the embodiment of FIG. 13 including a drug delivery systemincluding a drug delivery device in the form of an autoinjector, and theembodiment of FIGS. 14-16 including a drug delivery system including adrug delivery device in the form of an on-body injector or infuser.

Referring first to the drug delivery device of FIG. 13, the autoinjector700 includes a housing 710 in which may be disposed assemblies orstructures that insert or enable insertion of a cannula into thepatient, and that inject a drug or medicament from the reservoir throughthe cannula into the patient. According to certain embodiments, the sameassemblies or structures that insert the cannula into the patient mayalso allow flow of the drug or medicament from the reservoir through thecannula into the patient. The autoinjector 700 may also includeassemblies or structures that connect the cannula to the reservoir, thatwithdraw the cannula into the housing 710, or that deploy otherstructures that will prevent contact with the cannula once the cannulahas been removed from the patient. Further additional assemblies andstructures are also possible. The specific embodiment of theautoinjector 700 discussed below is thus by way of example and not byway of limitation. For example, the autoinjector 700 may lack assembliesor structures that insert the cannula (e.g., needle) into the patient,the insertion of the cannula into the patient resulting from the cannulabeing substantially fixed relative to the housing of the autoinjector700 and the autoinjector 700 being moved in the direction of thepatient.

The drug delivery system 700 includes a reservoir 712 and a cannula 714having a first end 716 that may be connected or connectable in fluidcommunication to the reservoir 712 and a second end 718 that may beinserted into a patient. The cannula 714 may be, for example, a rigidneedle having a beveled edge that may be sized such that the second end718 of the cannula 714 is received under the skin so as to deliver asubcutaneous injection of the drug within the reservoir 712. The firstend 716 of the cannula 714 may be disposed through a wall 720 of thereservoir 712, and thus be connected in fluid communication with thereservoir 712. As illustrated, the first end 716 of the cannula 714 maybe disposed only partially through the wall 720 (which wall 720 may be aresealable septum or stopper, for example) such that the first end ofthe cannula 714 may not be connected in fluid communication until thesecond end 718 of the cannula 714 is inserted into the patient. In sucha circumstance, the first end 716 of the cannula 714 may thus bedescribed as connectable in fluid communication with the reservoir 712,although it will be recognized that there are other mechanisms by whichthe first end 716 of the cannula 714 may be connectable, but notconnected, in fluid communication with the reservoir 712.

The drug delivery device 700 includes a shield 722 that may be deployedat least after the injection has been completed to limit access to thesecond end 718 of the cannula 714. According to certain embodiments, theshield 722 may have a biasing element 724 (such as a spring) thatextends the shield 722 from the housing 710 such that a distal end 726of the shield 722 extends beyond the second end 718 of the cannula 714except when the shield 722 is disposed against the skin and theinjection of the cannula 714 is actuated. In fact, the injection of thecannula 714 may be actuated according to certain embodiments of theautoinjector 700 by disposing the distal end 726 of the shield on oragainst the skin of the patient. The autoinjector 700 may also include alock 728 that is associated with the shield 722 and which limits themovement of the shield 722 relative to the housing 710 of theautoinjector 700 such that the distal end 726 of the shield 722 extendsfrom the housing 710 a sufficient distance to limit or prevent contactwith the second end 718 of the cannula 714 after the cannula 714 hasbeen removed from the skin of the patient after the drug has beendelivered.

The drug delivery device 700 also includes at least one drive 730 thatmay be used to insert the second end 718 of the cannula 714 into theskin of the patient, and to inject the drug or medicament from thereservoir 712 through the cannula 714 into the patient. The drive 730may include one or more springs, according to certain embodiments.According to other embodiments, the drive 730 may include a source ofpressurized gas or a source of a material that undergoes a phase change,such that the escaping gas or phase changing material provides a motiveforce that may be applied to the reservoir 712 to eject the drugtherefrom. According to still other embodiments, the drive 730 mayinclude an electromechanical system, such as may include a motor forexample, although such an electromechanical system may be moreappropriate for the on-body autoinjector or infuser described in greaterdetail below. Other embodiments for the drive 730 will be recognized.

The drive 730 may cooperate with a wall 732 of the reservoir 722 to movethat wall 732 toward the patient's skin. In accordance with such anembodiment, the wall 732 may be a stopper that is received within a bore734, and which may move along the bore 734 from a first end to a secondend to inject the drug from the reservoir 712. The drive 730 may alsocooperate with the stopper 732 and/or the bore 734 to move the reservoir712 relative to the housing 710 so as to move the second end 718 of thecannula 714 relative to the housing 710 and into the patient. Accordingto those embodiments wherein the drive 730 cooperates with the stopper732, this may occur before the first end 716 of the cannula 714 is influid communication with the reservoir 712. According to thoseembodiments wherein the drive cooperates with the bore 734, the drivemay include one component (e.g., first spring) that cooperates with thebore 734 to move the reservoir 712 and cannula 714 relative to thehousing 710, and a second component (e.g., second spring) thatcooperates with the stopper 732 to move the stopper 732 relative to thebore 734.

The drive 730 is associated with an actuator 740. The actuator 740activates the drive to cause the drive 730 to insert the cannula 714 andinject the drug from the reservoir 712 through the cannula 714 into thepatient. The actuator 740 may, according to certain embodiments, be theshield 722. According to other embodiments, such as the embodimentillustrated, the actuator 740 may be a button that may be depressed bythe user once the autoinjector 700 is disposed on or against thepatient's skin. While the embodiment illustrated in FIG. 13 has theactuator 740 disposed at one end of the device, the actuator 740 couldbe disposed on the side of the device as well.

As illustrated, the reservoir 712, biasing element 724, lock 728, andthe drive 730 are disposed within the housing 710, along with at leastpart of the cannula 714. Also disposed within the housing 710 is acontroller 750, a communication module 752, and at least one sensor orswitch. According to the embodiment illustrated, four sensors areincluded: a temperature sensor 760, a proximity sensor 762 (to determinethe presence of a needle cap (not shown) or the position of the needleshield 722) and two orientation sensors 764. In addition, a switch 766is also provided to determine if the button 740 has been depressed. Thecontroller 750 is coupled to the communication module 752, the sensors760, 762, 764 and the switch 766. The controller 750, communicationmodule 752, one or more of the sensors 760, 762, 764 and the switch 766may be packaged together as a single module, or each component may befabricated separately and coupled once the components are disposedwithin the housing 710. According to certain embodiments, each componentmay be integrated into the structure of the device 702 associated withthat component (e.g., the sensors 762, 764 may be integrated into theshield 722) and the location of the sensors in FIG. 12 is merelyillustrative.

The controller 750 may include at least one processor and memory. Thecontroller 750 may also include or be coupled to a power supply, e.g. abattery. The processor may be programmed to carry out the actions thatthe controller is adapted to perform and the memory may include one ormore tangible non-transitory readable memories having executableinstructions stored thereon, which instructions when executed by the atleast one processor may cause the at least one processor to carry outthe actions that the controller 750 is adapted to perform.Alternatively, the controller may include other circuitry that carriesout the actions that the controller is adapted to perform.

The communication module 752 may be any of a number of differentcommunication modules used to communicate with the mobile device 110and/or the computing device 114 (see FIG. 1). According to oneembodiment, the communication module 752 may be a Bluetooth/BluetoothLow Energy module that is on-board with the controller 750. Thecommunication module 752 is used to transmit information from theautoinjector 700 to the mobile device 110 or computing device 114.Alternatively, other protocols may be used by the communication module752, such as RFID, Zigbee, Wi-Fi, NFC, and others.

Given the presence of the temperature sensor 760, the proximity sensor762, the orientation sensors 764, and the switch 766, the controller 750may adapted or programmed to carry out most, of the method 300illustrated in FIGS. 3A-3C, as well as the methods illustrated in FIGS.5-7, 10 and 11, with the provision of suitable output devices, asrequired.

While the cannula 714 of the drug delivery system 300 illustrated inFIG. 13 is fixed relative to the reservoir 712 and thus in fluidcommunication with the reservoir 712 at all times, other embodiments maybe arranged differently, for example, with the cannula 714 being movablerelative to the reservoir 712. FIG. 13A illustrates a cannulasubassembly 780 which can be implemented in the drug delivery system 700of FIG. 13 and which allows the first end 716 of the cannula 714 to bemoved into fluid communication with the reservoir 712 when the secondend 718 of the cannula 714 is inserted into the patient, and to be movedout of fluid communication with the reservoir 712 when the second end718 of the cannula 714 is removed from the patient. To achieve thisfunctionality, the cannula subassembly 780 includes a spring seat 782fixed to the cannula 714 and a spring 784 positioned between the springseat 782 and the distal end of the reservoir 714. The spring seat 782may have a distal end surface 786 configured to be pressed against thepatient's skin and a proximal end surface 788 in contact with the spring784. As illustrated in FIG. 13A, the proximal end surface 788 mayinclude a guide channel or groove 790 to receive the distal end of thespring 784 and to prevent the spring 784 from sliding off of the springseat 782. Prior to delivery of the medicament to the patient, the spring784 may be in an un-compressed, natural state and bias the spring seat782 away from the reservoir 712, as seen in FIG. 13A. Accordingly, thefirst end 716 of the cannula 714 is spaced apart from the reservoir 712and not in fluid communication with the reservoir 712 when the spring784 is not compressed. When the drug delivery system 700 is used todeliver the medicament to the patient, the patient's skin pushes againstthe distal end surface 786 of the spring seat 782, thereby compressingthe spring 784 and moving the cannula 714 in the distal direction untilthe first end 716 of the cannula 714 penetrates the septum 720 andenters the interior of the reservoir 712. In this configuration, fluidcommunication is established between the cannula 714 and the reservoir712 so that the cannula 714 can deliver medicament in the reservoir 712to the patient. When the drug delivery system 700 is removed from thepatient's body, the spring 784 expands and returns to its natural,un-compressed state shown in FIG. 13A. As a result, the spring 784pushes the spring seat 786 away from the reservoir 712 and the first end716 of the cannula 714 is removed from the reservoir 712. Accordingly,the first end 716 of the cannula 714 is moved out of fluid communicationwith the reservoir 712. One benefit of the cannula subassembly 780depicted in FIG. 13A is that premature removal of the drug deliverydevice 700 from the patient's skin during medicament delivery is lesslikely to result in wasteful discharge of the medicament. This isbecause premature removal of the drug delivery system 700 from thepatient's skin causes the cannula subassembly 700 to automatically movedthe cannula 714 out of fluid communication with the reservoir 712.

FIG. 14 illustrates a drug delivery system 800. The system 800 may be awearable, disposable system. The system 800 may include a disposablehousing 802 that may be attached to a patient or wearer with adhesive,for example.

The disposable housing 802 may be made of a plastic material. As seen inFIG. 15, the housing 802 may be defined by two sections, a plate 804that is applied against the wearer's skin, and a dome 806 that isattached to the plate 804, preferably by a seal at an interface betweena peripheral edge 808 of the plate 804 and a peripheral edge 810 of thedome 806.

As shown in FIG. 15, the housing 802 has an interior surface 812defining an interior space 814, and an exterior surface 816. Inparticular, the plate 804 has an interior surface 818 and an exteriorsurface 820, and the dome 806 has an interior surface 822 and anexterior surface 824. According to the illustrated embodiment, theinterior surface 812 of the housing 802 is defined by the interiorsurfaces 818, 822 of the plate 804 and the dome 806, while the exteriorsurface 816 of the housing 802 is defined by the exterior surfaces 820,824 of the plate 804 and dome 806.

As noted above, the housing 802 may be attached to the skin of thewearer. In particular, an adhesive may be used. The adhesive may beadapted to releasably secure the housing to skin during a singleapplication. As shown in FIG. 15, the adhesive is disposed in a layer826 on a portion 828 of the exterior surface 816 of the housing 802, andin particular on the exterior surface 820 of the plate 804. The adhesiveis covered with a removable, disposable sheet 830 prior to applicationof the housing 802 to the skin of the wearer.

As seen in FIGS. 15 and 16, a reservoir 840, a drive 842, a cannula (orstructure, see below) 844, and an inserter 846 are disposed in thehousing 802. According to the illustrated embodiment, the reservoir 840may be defined at least in part by a combination of a rigid-walledcylinder or bore 860 having a port 862 at a first end 864 and a plunger866 fitted to move along a longitudinal axis 868 of the cylinder 860between a second end 870 and the first end 864 to force drug out of thereservoir 840 through the port 862 (FIG. 14). The movement of theplunger 866 may be caused by the operation of the drive 842.

The drive 842 may be similar in structure and operation to themechanisms for moving a plunger along a cylinder as may be found in U.S.Pat. Nos. 6,656,158; 6,656,159; 7,128,727; and 7,144,384, which patentsare incorporated by reference herein for all purposes. The drive 842 mayinclude a plunger arm, a motor, a transmission and a power supply (e.g.,a battery). The plunger arm may be in contact at least at a first endwith the plunger 866 to urge the plunger 866 along the cylinder 860, andthe transmission may be coupled to the plunger arm and the motor tocause the plunger arm to move according to the operation of the motor.The power supply provides a source of electrical power for the motor.The combination of the motor, transmission and power supply may also bereferred to as one example of an actuator. Other mechanisms, such assprings, pressurized gases, materials undergoing phase changes and thelike, may also be used to apply a force to the plunger to move theplunger along the cylinder.

According to other variants, a non-rigid collapsible pouch may besubstituted for the rigid-walled cylinder 860 and the plunger 866 shownin FIG. 15. It will be recognized that where the reservoir 860 is in theform of a non-rigid collapsible pouch, a spring-based mechanical systemmay be used to compress and pressurize the reservoir. According to stillfurther variants, a non-mechanical system may be used to move theplunger 866 or compress the bag. For example, a gas-generating systemmay be used, including a two-component system wherein the components arekept apart until the gas is to be generated, in which case they arecombined. As a further alternative, a swellable gel may be used, whereinthe introduction of water from a source internal to the device causesthe gel to increase in dimension to move the plunger or compress thepouch. As a further example, a propellant reservoir may be opened andthe propellant discharged to move the plunger 866 or compress the bag.Examples of such alternative mechanisms may be found in U.S. Pat. Nos.5,957,895; 5,858,001; and 5,814,020, which patents are incorporated byreference herein for all purposes.

According to certain embodiments, the reservoir 840 may be a pre-filledcontainer, such as a pre-filled cartridge or a pre-filled syringe.Alternatively, the delivery system 800 may include a fill port 880 influid communication with the reservoir 840, the fill port 880 adapted toreceive a luer tip of a syringe (e.g., syringe illustrated in FIG. 14),although a rubber septum may be used instead, for example. In use, ahealthcare provider may inject the drug from the syringe through thefill port 880 into the reservoir 840, and the syringe may be provided asa pre-filled syringe (filled with any of the materials mentioned above)to the healthcare provider with the delivery system 800 as a kit.

The cannula 844 may have a retracted state wherein a pointed end 890 (infact, the entire cannula 844) may be withdrawn inside the housing 802and a deployed state wherein the pointed end 890 projects from thehousing 802, the inserter 846 moving the needle 844 from the retractedstate to the deployed state. Examples of exemplary inserters may befound in U.S. Pat. Nos. 7,128,727 and 7,144,384, which patents areincorporated by reference herein for all purposes.

The cannula 844 may be hollow, and may be used to administer the drugdirectly to the patient. Alternatively, the structure 844 may be used inconjunction with a cannula 892, the structure 844 being used to insertthe cannula 892 into the patient through the injection site, and thedrug passing through the catheter 892 into the patient duringadministration. Phrased slightly differently, the system 800 may,according to certain exemplary embodiments, automatically insert a softcannula into the subcutaneous tissue.

As illustrated in FIG. 15, the housing 802 (specifically the plate 804)may have an aperture or opening 894 formed therein to permit the cannula(or structure) 844 (and optionally cannula 892) to pass therethrough.According to certain embodiments, the aperture 894 may be unobstructed,such that there is no impediment or obstacle to the movement of thecannula 844 (and catheter 892) through the opening 894. However, tobetter maintain the sterility of the cannula 844 and the device'scontainer closure integrity (CCI), a septum may be disposed in or overthe aperture 894.

The septum, which may be made of a rubber, may be disposed between thecannula 844 (and the space 814) and the patient's skin with the needle844 in the retracted state. In the deployed state, at least a portion ofthe needle 844 (i.e., the pointed end 890) will depend from the space814 through the septum. As such, the septum is always present as abarrier between the interior space 814 and the external environment.

The system 800 may also include a controller 900, which may include atleast one processor and memory, the processor programmed to carry outthe actions that the controller is adapted to perform and the memoryincluding one or more tangible non-transitory readable memories havingexecutable instructions stored thereon, which instructions when executedby the at least one processor may cause the at least one processor tocarry out the actions that the controller is adapted to perform.Alternatively, the controller may include other circuitry that carriesout the actions that the controller is adapted to perform. By way ofexample and not by way of limitation, the controller 900 may be adaptedto carry out any one of the methods described above relative to the drugdelivery system.

In addition to the controller 900, the system 800 may include acommunication module 902 and at least one sensor or switch. Thecommunication module 902 may be any of a number of differentcommunication modules used to communicate with the mobile device 110and/or the computing device 114 (see FIG. 1). According to oneembodiment, the communication module 902 may be a Bluetooth/BluetoothLow Energy module that is coupled to the controller 900. Thecommunication module 902 is used to transmit information from the system800 to the mobile device 110 or computing device 114. Alternatively,other protocols may be used by the communication module 752, such asRFID, Zigbee, Wi-Fi, NFC, and others. According to the embodimentillustrated, the system 800 also includes a temperature sensor 904 onboard the controller 900, and thus may carry out at least parts of themethods described in FIGS. 2 and 3A-3C.

While a small fraction of the number of possible sensors or sensingsystems have been mentioned above, further examples are provided below,grouped in accordance with the condition or operational states that maybe determined using these sensors or sensing systems.

Condition State Information, Generally

Temperature may be determined using a temperature sensitive paper thatchanges color upon receipt of thermal energy, the paper used inconjunction with an optical sensor that can sense the color or a colorchange. Temperature also may be determined using a thermocouple, forexample, with junctions against drug reservoir and external to device,the voltage across an in-line resistor being used to determine if thereservoir temperature or the ambient temperature is colder than that ofthe device and by how much. A reversible circuit may be used featuring amaterial such as nitinol that changes shape with temperature, thechanging shape closing the circuit thereby activating a cumulative timereach time a temperature threshold is exceeded, the cumulative time usedto ensure that the total time that the temperature exceeded a thresholdtemperature is below a predetermined threshold time period. A shapechange material may also be used to actuate a flag or a shield so as toreveal a readiness indicator, such as may be read using an opticaldevice.

Light exposure also may be determined using light sensitive paper thatchanges color with exposure to light, the paper used in conjunction withan optical device that can sense the color or a color change.Alternatively, a photoresistor with an associated voltage dividercircuit may be used to sense the presence of light.

Orientation of the drug delivery system (and device) might be determinedby using an accelerometer or a magnetometer. Additionally, the drugdelivery system may use two-way communication with a computing device,such as the mobile device 110, to obtain orientation information fromthe mobile device 110 and thereby infer the orientation of the drugdelivery device. In fact, the drug delivery system may be connected to amobile device 110 to improve the strength of the inference that theorientation of the mobile device 110 corresponds to the orientation ofthe drug delivery device.

The color and/or turbidity of the product may be measured using anoptical device, such as an optical transmitter/receiver pair, which pairmay be disposed on the same side of the reservoir or on opposite sidesof the reservoir. The measurement obtained using the optical devicerelative to the drug reservoir may be compared against a referencemeasurement. In fact, a reference may be provided within the drug deviceadjacent the drug reservoir such that the optical device may be used tooptically inspect the drug in the reservoir and the reference, so that acomparison may be made between, for example, the measurement obtainedrelative to the drug product in the reservoir and relative to thereference. Alternatively, any gap in the reception of the light beamtransmitted through the reservoir may indicate a cloudy product or onethat has undergone a color change, as may the reception (or failure ofreception) of a light beam that is deflected at a particular anglebecause of the presence of particulate matter in the product.Alternatively, a CCD array may be used to take a picture of the productin the reservoir, the picture being analyzed to determine color and/orturbidity, which analysis may be performed by the system or by a localdevice or a remote device (in which case the picture may be transmittedto the local or remote device for analysis).

Geographic position may be determined using Global Positioning Satellitetransceivers. Additionally, the drug delivery system may use two-waycommunication with a computing device, such as the mobile device 110, toobtain geographic position information from the mobile device 110 andinfer the position of the drug delivery device. In fact, the drugdelivery system may be connected to a mobile device 110 to improve thestrength of the inference that the position of the mobile device 110corresponds to the position of the drug delivery device.

Temporal information may be obtained using a timer that is started atthe time of manufacture, and which may be expiration date-calibrated.Alternatively, an RFID tag coded with manufacturing date may be includedin package or with device, and queried by system prior toadministration.

Operational State Information, Generally

The packaging may be used as a faraday cage, and the drug deliverysystem may include circuitry that detects interference with a signal orincreased received signals as a consequence of the removal of thepackaging so as to determine the operational state that the device isunpackaged.

A variety of sensors may be used to determine the operational state ofapplication to patient. For example, back EMF through a coil from movingmagnet on needle shield may indicate that the device has been applied tothe patient. Alternatively, displacement of component or assembly (suchas the needle shield) because of application of the drug delivery deviceto the patient may open or close a switch/circuit to signal thisoperational state. Along similar lines, the movement of components orassemblies may be detected using an optical sensor, with the light beambetween a transmitter and receiver being broken by a change in theposition of components, such as the needle shield or the reservoir(e.g., syringe or cartridge), upon application of the drug deliverydevice to the patient. As a further alternative, a capacitive orresistive sensor may be used, as may a pressure sensor. In fact,information regarding cannula (or needle) insertion may be determined bymeasuring the resistance through the needle and/or skin relative toexternal contact. Changes in temperature at the end of the drug deliverydevice intended to abut the patient's skin may also be used to determinethe operational state of application to the patient.

A similar set of sensors associated with the needle shield may be usedto determine when the needle shield has been deployed and locked inplace upon completion of drug delivery.

A similar set of sensors associated with the actuator or button (insteadof the needle shield) may be used to determine when the actuator orbutton has been depressed to trigger delivery of the drug.

An accelerometer may be used to sense the shock impulse of an actuatorbeing manipulated or the needle shield being moved to determine one ofthe operational states of triggering the device, initiating drugdelivery and completing drug delivery. A pressure sensor may be mountedin the reservoir to detect an increase in pressure in the reservoir thatwould occur upon initiation of drug delivery so as to be used todetermine this operational state. As a further alternative, a microphoneor audio sensor may be used to determine if the mechanical noises fromcomponents indicate activation of the device. As a still furtheralternative, a strain sensor may be mounted on a thin column betweendrive mechanism and plunger that will flex under force to sense theoperational state of triggering the drug device. In fact, according tocertain embodiments the strain sensor may be limited to a single use(i.e., the sensor fails or permanently deforms under flex) to “save” thefact that delivery was triggered thus eliminating the need for highfrequency signal monitoring.

Described below in connection with FIGS. 17-30 are additionalembodiments of sensors and sensing systems for detecting condition stateinformation and/or operational state information related to a drugdelivery device. While the sensors and sensing systems described beloware configured for use with an autoinjector, one or more of thesesensors and sensing systems may be configured for use with on-bodyinjector. Furthermore, any combination of the following sensors orsensing systems may be implemented in a single autoinjector or a singleon-body injector, or any other drug delivery device. Additionally, oneor more of the following sensors or sensing systems may be used incombination with one or more of the sensors or sensor systems describedabove in connection with FIGS. 1-16.

Referring to FIG. 17, illustrated is an embodiment of an autoinjector1700 configured to detect and report whether it has been triggered todeliver its medicament. The autoinjector 1700 includes a reservoir 1710configured to contain a medicament and a delivery cannula 1712 having aproximal end 1714 and a distal end 1716. The proximal end 1714 of thedelivery cannula 1712 is in fluid communication with the reservoir 1710,and the distal end 1716 of the delivery cannula 1712 is configured to bereceived within a patient. The autoinjector 1700 may also include aplunger 1720 moveable through the reservoir 1710 in a distal directionto discharge (e.g., eject) the medicament from the reservoir 1710 to thepatient via the delivery cannula 1712. In some embodiments, the plunger1720 may move linearly along a longitudinal axis A of the autoinjector1700. The longitudinal axis A may coincide with a longitudinal axis ofthe reservoir 1710. The plunger 1720 may have a proximal end 1722 and adistal end 1724 including a stopper 1726. The stopper 1726 may beconfigured to sealingly and slidably engage an inner wall of thereservoir 1710 so that the stopper 1726 can push medicament through thereservoir 1710 and into the delivery cannula 1712. Movement of theplunger 1720 may be accomplished through a drive mechanism 1730 such asa spring, electric motor, or any other element capable of providing amotive force for moving the plunger 1720 through the reservoir 1710. Insome embodiments, the plunger 1720 may be omitted, and the medicamentmay be discharged from the reservoir 1710 by way of pressurized air.

The autoinjector 1700 may further include an actuator 1740 configured totrigger the delivery of the medicament to the patient. As illustrated inFIG. 17, the actuator 1740 may be a button which can be manuallydepressed by the patient or a health care provider. In some embodiments,the actuator 1740 may be configured to activate the drive mechanism 1730to move the plunger 1720 in the distal direction to discharge themedicament from the reservoir 1710. In an embodiment where the drivemechanism 1730 includes a spring depressing the actuator 1740 mayrelease the spring so that it increases in length, thereby moving theplunger 1720 along the longitudinal axis A toward the distal end of theautoinjector 1700. In other embodiments, the actuator 1740 may be aswitch that activates a motor for moving the plunger 1720.

The autoinjector 1700 may also include a removable sterile barrier 1750disposed about the distal end 1716 of the delivery cannula 1712, and aneedle shield 1760 moveable relative to the distal end 1716 of thedelivery cannula 1712. The removable sterile barrier 1750 may beremovably attached to a distal end of the reservoir 1710. In someembodiments, the removable sterile barrier 1750 may form an interferenceor snap fit with the distal end of the reservoir 1710. A frictionalforce associated with the interference or snap fit may be overcome bymanually pulling the removable sterile barrier 1750 in a direction awayfrom a housing 1762 of the autoinjector 1700. The needle shield 1760 maybe biased in the distal direction by a biasing member 1764 (e.g., aspring).

In use, a patient or healthcare provider may initially remove theremovable sterile barrier 1750 from the autoinjector 1700 and press theneedle shield 1760 against the skin of the patient. The reaction forceexerted by the patient's skin may overcome the biasing force exerted bythe biasing member 1764, and thereby push the needle shield 1760 in theproximal direction, until the needle shield 1760 reaches a proximalposition inside the housing 1762. This action will expose the distal end1716 of the delivery cannula 1712 and cause it to pierce the skin of thepatient. Next, the patient or healthcare provider may depress theactuator 1740 to active the drive mechanism 1730 to move the plunger1720 in the distal direction. As a result, the plunger 1720 willdischarge the medicament from the reservoir 1710 to the patient via thedelivery cannula 1712. When delivery of the medicament is complete,and/or when the plunger 1720 has completed its delivery stroke, thepatient or healthcare provider may remove the autoinjector 1700 from theskin, thereby allowing the biasing member 1764 to move the needle shield1760 in the distal direction back to its distal position where it isdisposed about (i.e., surrounds) the distal end 1716 of the deliverycannula 1712.

Still referring to FIG. 17, the autoinjector 1700 may additionallyinclude a controller 1770 and a communication module 1772 coupled to thecontroller 1770. The controller 1770 and/or the communication module1772 may be disposed within the housing 1762 of the autoinjector 1700.The controller 1770 may include at least one processor (e.g., amicroprocessor) and at least one memory (e.g., a random access memory(RAM), a non-volatile memory such as a hard disk, a flash memory, aremovable memory, a non-removable memory, etc.). The controller 1770 mayalso include or be coupled to a power supply (e.g., a battery). The atleast one processor may be programmed to carry out the actions that thecontroller 1700 is configured to perform and the memory may include oneor more tangible non-transitory readable memories having executableinstructions stored thereon in the form of software, which instructionswhen executed by the at least one processor may cause the at least oneprocessor to carry out the actions that the controller 1770 isconfigured to perform. Alternatively, the controller 1700 may includeother circuitry that carries out the actions assigned to the controller1700. In some embodiments, the controller 1770 may only use hardware toexecute its tasks, thus avoiding the use of software.

The communication module 1772 may be coupled to the controller 1770 andmay be configured to transmit and/or receive information throughwireless and/or wired communications. The communication module 1772 maybe any of a number of different communication modules used tocommunicate with the mobile device 110 and/or the computing device 114(see FIG. 1). According to one embodiment, the communication module 1772may be a wireless transmitter that is on-board with the controller 1770such as a Bluetooth module or a Bluetooth Low Energy module. Thecommunication module 1770 may be used to transmit information from theautoinjector 1700 to the mobile device 110 or the computing device 114.Alternatively, other protocols may be used by the communication module1772, such as RFID, Zigbee, Wi-Fi, NFC, and others.

Referring to FIG. 17, the autoinjector 1700 may include a sensor 1780configured to detect movement of the actuator 1740. The sensor 1780 maybe coupled to the controller 1770 and configured to output a signal tothe controller 1770 indicating that the actuator 1740 has been moved.According to one embodiment, the sensor 1780 may be an electrical switch(e.g., a latching normally-open electrical switch) positioned so thatthe actuator 1740 contacts and closes the electrical switch when theactuator 1740 is depressed by the patient or healthcare provider. Byclosing the electrical switch, a closed electrical circuit may beformed, which in turn outputs an electrical signal to the controller1770. In response to the electrical signal, the controller 1770 maydetermine that the actuator 1770 has been used to trigger delivery ofthe medicament to the patient. The sensor 1780 is not limited to alatching normally-open electrical switch and may be any suitable sensorfor detecting movement of the actuator 1740 including a Pogo pin, anoptical sensor, a ferromagnetic proximity sensor, a pressure sensor,etc.

If the controller 1700 determines that the actuator 1740 has been usedto trigger delivery of the medicament to the patient, the controller1700 may generate a report representative of the triggering of theautoinjector 1700 and control the communication module 1772 to transmitthe report. In an embodiment where the communication module 1772includes a wireless transmitter, the controller 1770 may control thecommunication module 1772 to wirelessly transmit the report. In someembodiments, the report may be transmitted by the communication module1772 to an external mobile device (e.g., the mobile device 110) and/oran external computing device (e.g., the computing device 114).

Turning to FIGS. 18a-18c , illustrated is an embodiment of anautoinjector 1800 configured to detect and report delivery of amedicament from the reservoir to the patient. The autoinjector 1800 mayinclude some or all of the same components as the autoinjector 1700described above, including, for example, a reservoir 1810, a deliverycannula 1812 having a proximal end 1814 and a distal end 1816, a plunger1820 having a proximal end 1822 and a distal end 1824 including astopper 1826, a longitudinal axis A, an actuator 1840, a drive mechanism1830, a removable sterile barrier 1850, a needle shield 1860, a housing1862, a biasing member 1864, a controller 1870, and a communicationmodule 1872.

The autoinjector 1800 may further include a sensor 1880 configured todetect movement of the needle shield 1860. The sensor 1880 may becoupled to the controller 1870 and configured to output a signal to thecontroller 1870 indicating that the needle shield 1860 has been moved.According to one embodiment, the sensor 1880 may include an annularspring 1882 coupled to an outer circumferential surface of the needleshield 1860. Alternatively, the annular spring 1882 may be integrallyformed with the needle shield 1860 such that the annular spring 1882 andthe needle shield 1860 are a single component. The annular spring 1882may include radially protruding tabs 1884, 1886 configured to bereceived in respective apertures 1888, 1890 formed in the housing 1862of the autoinjector 1800. The radially protruding tabs 1884, 1886 may bearranged at diametrically opposed positions on the annular spring 1882,as shown in FIGS. 18b and 18c . In alternative embodiments, the housing1862 may include depressions, rather than apertures, for receiving theradially protruding tabs 1884, 1886. In terms of material, the annularspring 1882 may be made of an electrically conductive and elasticmaterial such as metal.

As illustrated in FIGS. 18a and 18b , when the needle shield 1860 isarranged at its distal position (i.e., where the needle shield 1860 isdisposed about the distal end 1816 of the delivery cannula 1812), theradially protruding tabs 1884, 1886 of the annular spring 1882 may bereceived in their respective apertures 1880, 1890 in the housing 1862.When the needle shield 1860 is pressed against the patient's skin andmoved in the proximal direction to its proximal position (see FIG. 18c), the radially protruding tabs 1884, 1886 of the annular spring 1882may slide out of their respective apertures 1888, 1890 and may be pushedradially inwardly by the inner wall of the housing 1862. Accordingly, agap may be formed between the annular spring 1882 and the inner wall ofthe housing 1862. After completion of the delivery of the medicament tothe patient and removal of the autoinjector 1800 from the patient'sskin, the biasing member 1864 may push the needle shield 1860 back toits distal position, thereby causing the radially protruding tabs 1884,1886 to slide along the inner surface of the housing 1862 until they arealigned with their respective apertures 1888, 1890. The annular spring1882 may expand radially outwardly such that the radially protrudingtabs 1884, 1886 are pushed into their respective apertures 1888, 1890(see FIG. 18b ). Accordingly, the gap between the annular spring 1882and the inner wall of the housing 1862 may be eliminated.

Referring to FIG. 18b , when the radially protruding tabs 1884, 1886 arereceived in their respective apertures 1888, 1890, an outer portion ofthe annular spring 1882 may be configured to contact a first electricalcontact 1892 and a second electrical contact 1894. As a result, a closedelectrical circuit may be formed between the first and second electricalcontacts 1892, 1894. This closed electrical circuit may output anelectrical signal to the controller 1870 via electrically conductivewires (not illustrated). In response to the electrical signal, thecontroller 1870 may determine that the needle shield 1860 is disposedabout the distal end 1816 of the delivery cannula 1862. Subsequently,the controller 1870 may generate a report representative of completionof a delivery of medicament from the reservoir 1810 to the patient, andcontrol the communication module 1872 to transmit the report. In anembodiment where the communication module 1872 includes a wirelesstransmitter, the controller 1870 may control the communication module1872 to wirelessly transmit the report. In some embodiments, the reportmay be transmitted by the communication module 1872 to an externalmobile device (e.g., the mobile device 110) and/or an external computingdevice (e.g., the computing device 114).

FIG. 19 illustrates an embodiment of an autoinjector 1900 configured todetect and report if a distal end of a delivery cannula has beeninserted into a patient. The autoinjector 1900 may include some or allof the same components as the autoinjector 1700 described above,including, for example, a reservoir 1910, a delivery cannula 1912 havinga proximal end 1914 and a distal end 1916, a plunger 1920 having aproximal end 1922 and a distal end 1924 including a stopper 1926, alongitudinal axis A, an actuator 1940, a drive mechanism 1930, aremovable sterile barrier 1950, a needle shield 1960, a housing 1962, abiasing member 1964, a controller 1970, and a communication module 1972.

The autoinjector 1900 may further include a sensor 1980 configured todetect movement of the needle shield 1960. The sensor 1980 may becoupled to the controller 1970 and configured to output a signal to thecontroller 1970 indicating that the needle shield 1960 has been moved.According to one embodiment, the sensor 1980 may include a washer 1982made of an electrically conductive material such as metal. The washer1982 may be coupled to a proximal axial end surface of the needle shield1960 as shown in FIG. 19. The washer 1982 may have an annular shape witha central aperture so that the reservoir 1910 can pass through thewasher 1982.

When the needle shield 1960 is pressed against the patient's skin andmoved in the proximal direction to its proximal position, the washer1982 may contact a first electrical contact 1992 and a second electricalcontact 1994, thereby forming a closed electrical circuit between thefirst and second electrical contacts 1992, 1994. This closed electricalcircuit may output an electrical signal to the controller 1970 viaelectrically conductive wires. In response to the electrical signal, thecontroller 1970 may determine that the needle shield 1960 has been movedrelative to the distal end 1916 of the delivery cannula 1912.Subsequently, the controller 1970 may generate a report representativeof completion of the insertion of the distal end 1916 of the deliverycannula 1912 into the patient, and control the communication module 1972to transmit the report. In an embodiment where the communication module1972 includes a wireless transmitter, the controller 1970 may controlthe communication module 1972 to wirelessly transmit the report. In someembodiments, the report may be transmitted by the communication module1972 to an external mobile device (e.g., the mobile device 110) and/oran external computing device (e.g., the computing device 114).

FIG. 20 illustrates another embodiment of an autoinjector 2000configured to detect and report if a distal end of a delivery cannulahas been inserted into a patient. The autoinjector 2000 may include someor all of the same components as the autoinjector 1700 described above,including, for example, a reservoir 2010, a delivery cannula 2012 havinga proximal end 2014 and a distal end 2016, a plunger 2020 having aproximal end 2022 and a distal end 2024 including a stopper 2026, alongitudinal axis A, an actuator 2040, a drive mechanism 2030, aremovable sterile barrier 2050, a needle shield 2060, a housing 2062, abiasing member 2064, a controller 2070, and a communication module 2072.

The autoinjector 2000 may further include a sensor 2080 configured todetect movement of the needle shield 2060. The sensor 2080 may becoupled to the controller 2070 and configured to output a signal to thecontroller 2070 indicating that the needle shield 2060 has been moved.According to one embodiment, the sensor 2080 may include a Pogo pin 2082fixed to the inner wall of the housing 2062.

When the needle shield 2060 is pressed against the patient's skin andmoved in the proximal direction to its proximal position, the Pogo pin2082 may contact and/or be depressed by a proximal axial end surface ofthe needle shield 2060, thereby creating a closed electrical circuit.This closed electrical circuit may output an electrical signal to thecontroller 2070. An electrically conductive wire (not illustrated) maycouple the Pogo pin 2082 to the controller 2070. In response to theelectrical signal, the controller 2070 may determine that the needleshield 2060 has been moved relative to the distal end 2016 of thedelivery cannula 2012. Subsequently, the controller 2070 may generate areport representative of the completion of insertion of the distal end2016 of the delivery cannula 2012 into the patient, and control thecommunication module 2072 to transmit the report. In an embodiment wherethe communication module 2072 includes a wireless transmitter, thecontroller 2070 may control the communication module 2072 to wirelesslytransmit the report. In some embodiments, the report may be transmittedby the communication module 2072 to an external mobile device (e.g., themobile device 110) and/or an external computing device (e.g., thecomputing device 114).

Turning to FIGS. 21a and 21b , illustrated is another embodiment of anautoinjector 2100 configured to detect and report delivery of amedicament from the reservoir to the patient. The autoinjector 2100 mayinclude some or all of the same components as the autoinjector 1700described above, including, for example, a reservoir 2110, a deliverycannula 2112 having a proximal end 2114 and a distal end 2116, a plunger2120 having a proximal end 2122 and a distal end 2124 including astopper 2126, a longitudinal axis A, an actuator 2140, a drive mechanism2130, a removable sterile barrier 2150, a needle shield 2160, a housing2162, a biasing member 2164, a controller 2170, and a communicationmodule 2172.

The autoinjector 2100 may further include a sensor 2180 configured todetect movement of the plunger 2120. The sensor 2180 may be coupled tothe controller 2170 and configured to output a signal to the controller2170 indicating that the plunger 2120 has been moved. According to oneembodiment, the sensor 2180 may include an optical sensor 2182 fixed toan inner wall of the needle shield 2160 as illustrated in FIGS. 21a and21b . The optical sensor 2182 may be configured to detect infrared lightradiating from one or more objects such as the stopper 2126. The opticalsensor 2182 may have a field of view 2184 within which it can detect theexistence one or more objects. The optical sensor 2182 may also beconfigured to output a signal to the controller 2170 that isrepresentative of a distance between the optical sensor 2182 and anobject in its field of view 2184.

As seen in FIG. 21a , prior to activation of the plunger 2120, thestopper 2126 may be outside the field of view 2184 of the optical sensor2182. Thus, the optical sensor 2182 may output a signal, or no signal,to the controller 2170, which may in turn determine that the delivery ofthe medicament from the reservoir to the patient has not been completed.The controller 2170 may control the communication module 2172 totransmit (e.g., wirelessly transmit) a report representative of thedetermination that delivery of the medicament has not been completed toan external computing system.

FIG. 21b shows the plunger 2120 in the process of moving through thereservoir 2110 to deliver the medicament to the patient but has not yetcompleted its delivery stroke. At this stage, the stopper 2126 may be inthe field of view 2184 of the optical sensor 2182. Accordingly, theoptical sensor 2182 may output a signal to the controller 2170indicative of the distance between the optical sensor 2182 and thestopper 2126. The controller 2170 may compare the measured distance witha threshold distance to determine if the measured distance is less thanor equal to the threshold distance. In the configuration shown in FIG.21b , the measured distance would be greater than or equal to thethreshold distance. Accordingly, the controller 2170 would determinethat the plunger 2120 has not completed its delivery stroke and generatea report representative of the fact that delivery of the medicament tothe patient has not been completed. The controller 2170 may control thecommunication module 2172 to transmit (e.g., wirelessly transmit) thereport to an external computing system.

FIG. 21c depicts the plunger 2120 having completed its delivery strokesuch that delivery of the medicament to the patient is completed. Here,the stopper 2126 may be in the field of view 2184 of the optical sensor2182 and the optical sensor 2182 may therefore output a signal to thecontroller 2170 indicative of the distance between the optical sensor2182 and the stopper 2126. The controller 2170 may compare the measureddistance with the threshold distance to determine if the measureddistance is less than or equal to the threshold distance. In theconfiguration shown in FIG. 21c , the measured distance would be lessthan or equal to the threshold distance. Accordingly, the controller2170 would determine that the plunger has completed its delivery strokeand generate a report representative of completion of the delivery ofthe medicament to the patient. The controller 2170 may control thecommunication module 2172 to transmit (e.g., wirelessly transmit) thereport to an external computing system.

In an alternative embodiment, the optical sensor 2182 may be fixed to aninner wall of the housing 2162 proximal to the needle shield 2160. Insuch an embodiment, the controller 2170 may evaluate whether themeasured distance is greater than or equal to a threshold distance inorder to determine whether or not the plunger has completed its deliverystroke.

FIG. 22a-22c illustrate another embodiment of an autoinjector 2200configured to detect and report delivery of a medicament from thereservoir to the patient. The autoinjector 2200 may include some or allof the same components as the autoinjector 1700 described above,including, for example, a reservoir 2210, a delivery cannula 2212 havinga proximal end 2214 and a distal end 2216, a plunger 2220 having aproximal end 2222 and a distal end 2224 including a stopper 2226, alongitudinal axis A, an actuator 2240, a drive mechanism 2230, aremovable sterile barrier 2250, a needle shield 2260, a housing 2262, abiasing member 2264, a controller 2270, and a communication module 2272.

The autoinjector 2200 may further include a sensor 2280 configured todetect movement of the plunger 2220. The sensor 2280 may be coupled tothe controller 2270 and configured to output a signal to the controller2270 indicating that the plunger 2220 has been moved. According to oneembodiment, the sensor 2280 may include a first electrically conductivemember 2282 spaced apart from the plunger 2220 and a second electricallyconductive member 2284 coupled to the plunger 2220 such that the secondelectrically conductive member 2284 moves together with the plunger2220. The second electrically conductive member 2284 may be configuredto slidably engage the first electrically conductive member 2282 duringmovement of the plunger 2220 prior to completion of the delivery strokeby the plunger 2220 (see FIG. 22a ). While the first and secondelectrically conductive members 2282, 2284 are engaged, the first andsecond electrically conductive members 2282, 2284 may form a closedelectrical circuit that outputs a signal to the controller 2270. Uponcompletion of the delivery stroke by the plunger 2220 (see FIG. 22b ),the second electrically conductive member 2284 may disengage from thefirst electrically conductive member 2282 such that the first and secondelectrically conductive members 2282, 2284 no longer contact each other.As a result, an open electrical circuit may be formed, and consequently,no signal may be outputted from the sensor 2280 to the controller 2270.

In response to the lack of a signal from the sensor 2280, the controller2270 may determine that the plunger 2220 has completed its deliverystroke and generate a report representative of completion of delivery ofthe medicament to the patient. The controller 2270 may control thecommunication module 2272 to transmit (e.g., wirelessly transmit) thereport to an external computing system. In an embodiment where thecommunication module 2272 includes a wireless transmitter, thecontroller 2270 may control the communication module 2272 to wirelesslytransmit the report. In some embodiments, the report may be transmittedby the communication module 2272 to an external mobile device (e.g., themobile device 110) and/or an external computing device (e.g., thecomputing device 114).

As depicted in FIG. 22c , the first electrically conductive member 2282may include a spring-biased clip 2290 fixed to the housing 2262 of theautoinjector 2200, and the second electrically conductive member 2284may include a wire 2292 fixed to and moveable together with the plunger2220. The wire 2292 may be dragged behind the plunger 2220 as theplunger 2220 is moved in the distal direction to discharge themedicament from the reservoir 2210. The spring-biased clip 2290 may beconfigured to slidably grasp the wire 2292 as the wire 2292 translates.The length of the wire 2292 may be such that, when the plunger 2220reaches its most distal position and thus completes the delivery stroke,the wire 2292 may not be long enough to reach the spring-based clip2290. As a result, the wire 2292 may disengage from the spring-biasedclip 2290, thereby forming the open electrical circuit.

Turning to FIGS. 23a and 23b , illustrated is an embodiment of anautoinjector 2300 configured to detect and a report an amount ofmedicament delivered to the patient. The autoinjector 2300 may includesome or all of the same components as the autoinjector 1700 describedabove, including, for example, a reservoir 2310, a delivery cannula 2312having a proximal end 2314 and a distal end 2316, a plunger 2320 havinga proximal end 2322 and a distal end 2324 including a stopper 2326, alongitudinal axis A, an actuator 2340, a drive mechanism 2330, aremovable sterile barrier 2350, a needle shield 2360, a housing 2362, abiasing member 2364, a controller 2370, and a communication module 2372.

The autoinjector 2200 may further include a sensor 2380 configured todetect movement of the plunger 2320. The sensor 2380 may be coupled tothe controller 2370 and configured to output a signal to the controller2370 indicating that the plunger 2320 has been moved and/or the traveldistance of the plunger 2320. According to one embodiment, the sensor2380 may include a variable resistor 2382 having an adjustableelectrical resistance R_(x). The electrical resistance R_(x) of thevariable resistor 2382 may be proportional to a length of the variableresistor 2382 through which an electric current must travel beforereaching the controller 2370. In some embodiments, the electricalresistance R_(x) of the variable resistor 2382 may increase as thelength of the electric current path through the variable resistor 2382increases, and the electrical resistance R_(x) of the variable resistor2382 may decrease as the length of the current path through the variableresistor 2382 decreases.

To change the length of the current path through the variable resistor2382, an electrically conductive member 2384 may slidably engage thevariable resistor 2382 as shown in FIG. 23a . The electricallyconductive member 2384 may be coupled to the plunger 2320 such that theelectrically conductive member 2384 moves together with the plunger2320. Thus, movement of the plunger 2320 may cause the electricallyconductive member 2384 to slide along the variable resistor 2382. Thismay change the length of the current path through the variable resistor2382. Accordingly, movement of the plunger 2320 may result in a changeto the electrical resistance R_(x) of the variable resistor 2382.

In the configuration shown in FIG. 23a , movement of the plunger 2320 inthe distal direction toward the distal end of the autoinjector 2300increases the length of the electrical path through the variableresistor 2382, thereby increasing the electrical resistance R_(x). Thecontroller 2370 may be configured to correlate the electrical resistanceR_(x) to the travel distance of the plunger 2320 and/or the amount ofmedicament delivered to the patient. In some embodiments, the controller2370 may be configured to measure the time period over which theelectrical resistance R_(x) changes, and correlate this time period tothe speed by which the medicament is delivered to the patient.Subsequently, the controller 2370 may generate a report representativeof the amount of medicament delivered to the patient and/or the speed ofdelivery, and control the communication module 2372 to transmit (e.g.,wirelessly transmit) the report to an external computing system. In anembodiment where the communication module 2372 includes a wirelesstransmitter, the controller 2370 may control the communication module2372 to wirelessly transmit the report. In some embodiments, the reportmay be transmitted by the communication module 2372 to an externalmobile device (e.g., the mobile device 110) and/or an external computingdevice (e.g., the computing device 114).

FIG. 23b is a circuit diagram illustrating one example an electricalcircuit including the controller 2370 and the variable resistor 2382depicted in FIG. 23a . As shown in FIG. 23b , the controller 2370 may bearranged in parallel with a resistor R₁. In this circuit, V_(in) may beequal to V_(out)*((R_(x)/(R_(x)+R₁)). Thus, as the electrical resistanceR_(x) of the variable resistor 2382 increases, V_(in) may increase, andvice versa. The controller 2370 may correlate V_(in) to the traveldistance of the plunger 2320 and/or the amount of medicament deliveredto the patient.

FIGS. 24a and 24b depict yet another embodiment of an autoinjector 2400configured to detect and report delivery of a medicament from thereservoir to the patient. The autoinjector 2400 may include some or allof the same components as the autoinjector 1700 described above,including, for example, a reservoir 2410, a delivery cannula 2412 havinga proximal end 2414 and a distal end 2416, a plunger 2420 having aproximal end 2422 and a distal end 2424 including a stopper 2426, alongitudinal axis A, an actuator 2440, a drive mechanism 2430, aremovable sterile barrier 2450, a needle shield 2460, a housing 2462, abiasing member 2464, a controller 2470, and a communication module 2472.

The autoinjector 2400 may further include a sensor 2480 configured todetect movement of the plunger 2420. The sensor 2480 may be coupled tothe controller 2470 and configured to output a signal to the controller2470 indicating that the plunger 2420 has been moved. According to oneembodiment, the sensor 2480 may include a first electrically conductivemember 2482 spaced apart from the plunger 2420 and a second electricallyconductive member 2484 coupled to the plunger 2420 such that the secondelectrically conductive member 2484 moves together with the plunger2420. The first electrically conductive member 2482 may be a deflectableelectrical contact fixed to, and extending inwardly from, an inner wallof the housing 2462. The electrically conductive member 2484 may be aspring retainer lip that is fixed to the plunger 2420.

As seen in FIG. 24b , the second electrically conductive member 2484 maybe configured to engage the first electrically conductive member 2482 toform a closed electrical circuit when the plunger 2420 has completed itsdelivery stroke. This closed electrical circuit may output a signal tothe controller 2470. Prior to completion of the delivery stroke, thesecond electrically conductive member 2484 may be disengaged (e.g.,spaced apart) from the first electrically conductive member 2482 so thatan open electrical circuit is formed, and thus no signal is outputted tothe controller 2470.

In response to the electrical signal created by engagement of the firstand second electrically conductive members 2482, 2484, the controller2470 may determine that the plunger 2420 has completed its deliverystroke and generate a report representative of the completion ofdelivery of the medicament to the patient. The controller 2470 maycontrol the communication module 2472 to transmit (e.g., wirelesslytransmit) the report to an external computing system. In an embodimentwhere the communication module 2472 includes a wireless transmitter, thecontroller 2470 may control the communication module 2472 to wirelesslytransmit the report. In some embodiments, the report may be transmittedby the communication module 2472 to an external mobile device (e.g., themobile device 110) and/or an external computing device (e.g., thecomputing device 114).

FIGS. 25a and 25b illustrate another embodiment of an autoinjector 2500configured to detect and report delivery of a medicament from thereservoir to the patient. The autoinjector 2500 may include some or allof the same components as the autoinjector 1700 described above,including, for example, a reservoir 2510, a delivery cannula 2512 havinga proximal end 2514 and a distal end 2516, a plunger 2520 having aproximal end 2525 and a distal end 2525 including a stopper 2526, alongitudinal axis A, an actuator 2540, a drive mechanism 2530, aremovable sterile barrier 2550, a needle shield 2560, a housing 2562, abiasing member 2564, a controller 2570, and a communication module 2572.

The autoinjector 2500 may further include a sensor 2580 configured todetect movement of the plunger 2520. The sensor 2580 may be coupled tothe controller 2570 and configured to output a signal to the controller2570 indicating that the plunger 2520 has been moved. According to oneembodiment, the sensor 2580 may be a resistor R_(s) that is electricallyconnected in series with a spring 2584 and a voltage source V_(s). FIGS.25a and 25b depict the resistor R_(s) and the voltage source V_(s) inschematic form and thus do not represent the actual locations orphysical configurations of the resistor R_(s) and the voltage sourceV_(s). In reality, the resistor R_(s) and the voltage source V_(s) maybe contained with the housing 2562 of the autoinjector 2500.

The spring 2584 may correspond to the drive mechanism 2530 and thus maybe responsible for moving the plunger 2520 in the distal direction tocomplete its delivery stroke. When released (for example, by depressionof the actuator 2540), the spring 2530 may increase in length, fromlength L₁ (see FIG. 25a ) to length L₂ (see FIG. 25b ), thereby pushingthe plunger 2520 in the distal direction and discharging the medicamentfrom the reservoir 2510. The spring 2584 may have a plurality ofhelically-wound coils, with each adjacent pair of the coils beingseparated by a distance. The spring 2584 may behave like an inductor byvirtue of its multiple coils. The inductance of the spring 2584 may varyaccording to the distance between each adjacent pair of the coils. Insome embodiments, increasing the length of the spring 2584 from lengthL₁ to length L₂ may increase the distance between each adjacent pair ofthe coils and thereby decrease the inductance associated with the spring2584. In such embodiments, the inductance of the spring 2584 may beinversely proportional to the length of the spring 2584. Moreover, insuch embodiments, the inductance of the spring 2584 may be inverselyproportional to the distance between each adjacent pair of the coils. Asa result of a change in the inductance of the spring 2584, an electriccurrent through the resistor R_(s) may change. The changing electriccurrent through the resistor R_(s) may be measured by the controller2570 (e.g., by having the controller 2570 measure a voltage drop acrossthe resistor R_(s)).

In response to a change in the electric current flowing through theresistor R_(s), the controller 2570 may determine that the plunger 2520has completed its delivery stroke and generate a report representativeof the completion of delivery of the medicament to the patient. Thecontroller 2570 may control the communication module 2572 to transmit(e.g., wirelessly transmit) the report to an external computing system.In an embodiment where the communication module 2572 includes a wirelesstransmitter, the controller 2570 may control the communication module2572 to wirelessly transmit the report. In some embodiments, the reportmay be transmitted by the communication module 2572 to an externalmobile device (e.g., the mobile device 110) and/or an external computingdevice (e.g., the computing device 114).

FIG. 26 illustrates another embodiment of an autoinjector 2600configured to detect and report delivery of a medicament from thereservoir to the patient. The autoinjector 2600 may include some or allof the same components as the autoinjector 1700 described above,including, for example, a reservoir 2610, a delivery cannula 2612 havinga proximal end 2614 and a distal end 2616, a plunger 2620 having aproximal end 2626 and a distal end 2626 including a stopper 2626, alongitudinal axis A, an actuator 2640, a drive mechanism 2630, aremovable sterile barrier 2650, a needle shield 2660, a housing 2662, abiasing member 2664, a controller 2670, and a communication module 2672.

The autoinjector 2600 may further include a sensor 2680 configured todetect movement of the plunger 2620. The sensor 2680 may be coupled tothe controller 2670 and configured to output a signal to the controller2670 indicating that the plunger 2620 has been moved. According to oneembodiment, the sensor 2680 may be a ferromagnetic proximity sensor 2682configured to output a signal indicative of the presence or absence of ametal plunger rod 2584 at a predetermined location within theautoinjector 2600.

As illustrated in FIG. 26, the ferromagnetic proximity sensor 2682 maybe fixed to an inner wall of the housing 2662. The ferromagneticproximity sensor 2682 may be positioned so that the metal plunger rod2684 is advanced past the ferromagnetic proximity sensor 2682 when theplunger 2620 has completed its delivery stroke, as seen in FIG. 26. As aresult, the ferromagnetic proximity sensor 2682 may detect an absence ofthe metal plunger rod 2684. On the other hand, prior to completion ofthe delivery stroke, the metal plunger rod 2684 may be aligned withferromagnetic proximity sensor 2682 such that the ferromagneticproximity sensor 2682 detects the presence of the metal plunger rod2684.

In response to a signal from the ferromagnetic proximity sensor 2682indicating the absence of the metal plunger rod 2684, or in response tothe absence of a signal from the ferromagnetic proximity sensor 2682indicating the presence of the metal plunger rod 2684, the controller2670 may determine that the plunger 2620 has completed its deliverystroke and generate a report representative of the completion of thedelivery of the medicament to the patient. The controller 2670 maycontrol the communication module 2672 to transmit (e.g., wirelesslytransmit) the report to an external computing system. In an embodimentwhere the communication module 2672 includes a wireless transmitter, thecontroller 2670 may control the communication module 2672 to wirelesslytransmit the report. In some embodiments, the report may be transmittedby the communication module 2672 to an external mobile device (e.g., themobile device 110) and/or an external computing device (e.g., thecomputing device 114).

FIGS. 27a-e illustrate another embodiment of an autoinjector 2700configured to detect and report an amount of medicament delivered to thepatient. The autoinjector 2700 may include some or all of the samecomponents as the autoinjector 1700 described above, including, forexample, a reservoir 2710, a delivery cannula 2712 having a proximal end2714 and a distal end 2716, a plunger 2720 having a proximal end 2722and a distal end 2724 including a stopper 2726, a longitudinal axis A,an actuator 2740, a drive mechanism 2730, a removable sterile barrier2750, a needle shield 2760, a housing 2762, a biasing member 2764, acontroller 2770, and a communication module 2772.

The autoinjector 2700 may further include a sensor 2780 configured todetect movement of the plunger 2720. The sensor 2780 may be coupled tothe controller 2770 and configured to output a signal to the controller2770 indicating that the plunger 2720 has been moved and/or the traveldistance of the plunger 2720. According to one embodiment, the sensor2780 may be comprised of a plurality of photoresistors 2782 a-d. Theelectrical resistance of each of the photoresistors 2782 a-d maydecrease with increasing incident light intensity. As depicted in FIG.27a , the photoresistors 2782 a-d may be arranged adjacent one anotherand parallel to the longitudinal axis A of the autoinjector 2700. Thephotoresistors 2782 a-d may be fixed to the exterior of the reservoir2710.

To permit ambient light to be incident upon the photoresistors 2782 a-d,the housing 2762 of the autoinjector 2700 may include one or morewindows 2784 a and 2784 b as shown in FIG. 27b . The plunger 2720,including the stopper 2726, may be made of an opaque material such thatthe plunger 2720 obstructs the ambient light shining through the windows2784 a and 2784 b as the plunger 2720 is advanced through the reservoir2710 in the distal direction along the longitudinal axis A. The plunger2720 may be outfitted with an opaque sleeve 2786 as shown in FIG. 27afor this purpose. The further the plunger 2720 is advanced in the distaldirection, the more the windows 2784 a and 2784 b are covered. Thus,advancing the plunger 2720 in the distal direction along thelongitudinal axis A may reduce the ambient light incident on each of theplurality of photoresistors 2782 a-d in a sequential order. For example,as shown in FIG. 27c , when the plunger 2720 has completed approximatelyhalf of its delivery stroke, ambient light may be prevented fromreaching the photoresistors 2782 a and 2782 b, whereas ambient light maystill be incident on each of the photoresistors 2782 c and 2782 d. Thelack of ambient light incident on the photoresistors 2782 a and 2782 bmay cause the electrical resistance of each of these photoresistors toincrease, potentially even causing each of the photoresistors 2782 a and2782 b to stop conducting electrical current. On the other hand, thephotoresistors 2782 c and 2782 d, which are still exposed to ambientlight, may exhibit a low electrical resistance and continue to conductelectrical current. When the plunger 2720 completes its delivery strokeas shown in FIG. 27d , all ambient light through the windows 2784 a and2784 b may be obstructed, thereby causing a substantial increase in theelectrical resistance of all of the photoresistors 2782 a-d.

FIG. 27e is a circuit diagram illustrating one example of an electricalcircuit including the controller 2770 and the photoresistors 2782 a-d.The electrical circuit may include a resistor R₂ having a known constantelectrical resistance. The photoresistors 2782 a-d may be arranged inparallel with the controller 2770. The controller 2770 may be able tomeasure the voltage drop across all of the photoresistors 2782 a-d andthus compute their total effective electrical resistance. In someembodiments, the controller 2770 may be configured to individuallydetermine the electrical resistance of each of the photoresistors 2782a-d. Also, in some embodiments, the autoinjector 2700 may include areference photoresistor 2790 located on the exterior of the housing 2762of the autoinjector, in order to calibrate the controller 2770 for thenatural intensity of the ambient light.

The controller 2770 may correlate the electrical resistance of one ormore of the photoresistors 2782 a-d to the travel distance of theplunger 2720 and/or the amount of medicament delivered to the patient.In some embodiments, the controller 2770 may be configured to measurethe time period over which the electrical resistance of one or more ofthe photoresistors 2782 a-d changes, and then correlate this time periodto the speed by which the medicament was delivered to the patient.Subsequently, the controller 2770 may generate a report representativeof the amount of medicament delivered to the patient and/or the speed ofdelivery, and control the communication module 2772 to transmit (e.g.,wirelessly transmit) the report to an external computing system. In anembodiment where the communication module 2772 includes a wirelesstransmitter, the controller 2770 may control the communication module2772 to wirelessly transmit the report. In some embodiments, the reportmay be transmitted by the communication module 2772 to an externalmobile device (e.g., the mobile device 110) and/or an external computingdevice (e.g., the computing device 114).

FIG. 28 depicts yet another embodiment of an autoinjector 2800configured to detect and report the amount of medicament delivered to apatient. The autoinjector 2800 may include some or all of the samecomponents as the autoinjector 1700 described above, including, forexample, a reservoir 2810, a delivery cannula 2812 having a proximal end2814 and a distal end 2816, a plunger 2820 having a proximal end 2822and a distal end 2824 including a stopper 2826, a longitudinal axis A,an actuator 2840, a drive mechanism 2830, a removable sterile barrier2850, a needle shield 2860, a housing 2862, a biasing member 2864, acontroller 2870, and a communication module 2872.

The autoinjector 2800 may further include a sensor 2880 configured todetect movement of the plunger 2820. The sensor 2880 may be coupled tothe controller 2870 and configured to output a signal to the controller2870 indicating the presence or absence of fluid at various levelswithin the reservoir 2810. According to one embodiment, the sensor 2880may include a capacitive fluid level sensor 2882 coupled to an exteriorof the reservoir 2810. In some embodiments, the capacitive fluid levelsensor 2882 may be oriented such that its longitudinal axis is parallelto the longitudinal axis of the reservoir. Therefore, as the fluid levelwithin the reservoir 2810 decreases, the capacitive fluid level sensor2882 may be gradually uncovered.

In response to the signal from the sensor 2880, the controller 2870 maydetermine an amount of medicament remaining in the reservoir 2810 and/orgenerate a report representative of an amount of medicament delivered tothe patient from the reservoir based on the amount of medicamentremaining in the reservoir. The controller 2870 may control thecommunication module 2872 to transmit (e.g., wirelessly transmit) thereport to an external computing system. In an embodiment where thecommunication module 2872 includes a wireless transmitter, thecontroller 2870 may control the communication module 2872 to wirelesslytransmit the report. In some embodiments, the report may be transmittedby the communication module 2872 to an external mobile device (e.g., themobile device 110) and/or an external computing device (e.g., thecomputing device 114).

FIGS. 29a and 29b depict an embodiment of an autoinjector 2900configured to detect and report contact between a housing of theautoinjector 200 and the patient. The autoinjector 2900 may include someor all of the same components as the autoinjector 1700 described above,including, for example, a reservoir 2910, a delivery cannula 2912 havinga proximal end 2914 and a distal end 2916, a plunger 2920 having aproximal end 2922 and a distal end 2924 including a stopper 2926, alongitudinal axis A, an actuator 2940, a drive mechanism 2930, aremovable sterile barrier 2950, a needle shield 2960, a housing 2962, abiasing member 2964, a controller 2970, and a communication module 2972.

The autoinjector 2900 may further include a sensor 2980 configured todetect contact between the housing 2962 and an object (e.g., the skin ofa patient or the clothing of the patient). The sensor 2980 may becoupled to the controller 2970 and configured to output a signal to thecontroller 2970 indicative of contact with the object. According to oneembodiment, the sensor 2980 may include a first electrically conductivemember 2982 coupled to an axial end face of the distal end of thehousing 2962 and a second electrically conductive member 2984 coupled toan axial end face of the distal end of the needle shield 2960. In someembodiments, the first and second electrically conductive members 2982,2984 may each include an electrically conductive adhesive. The firstelectrically conductive member 2982 may be spaced apart from the secondelectrically conductive member 2984 so that the first and secondelectrically conductive members 2982, 2984 do not physically contacteach other, at least when the needle shield 2960 is biased by thebiasing member 2964 to its distal position as shown in FIG. 29 a.

As seen in FIG. 29b , when the needle shield 2960 is pressed against theskin 2990 of the patient 2992, the needle shield 2960 may be pushed intothe housing 2962 to its proximal position, and the first electricallyconductive member 2982 may move into contact with the skin 2990 of thepatient 2992. Thus, both the first and second electrically conductivemembers 2982, 2984 may contact the skin 2990 of the patient 2992 whenthe needle shield 2960 is pressed against the skin 2990 of the patient2990.

The skin 2990 of the patient 2992 may conduct electricity between thefirst and second electrically conductive members 2982, 2984.Consequently, a closed electrical circuit may be formed between thefirst and second electrically conductive members 2982, 2984 when boththe first and second electrically conductive members 2982, 2984 are incontact with the skin 2990 of the patient 2992. This closed electricalcircuit may output a signal to the controller 2970.

In response to the signal from the sensor 2280, the controller 2970 maydetermine that the housing 2962 contacts the patient, and generate areport representative of contact between the housing 2962 and thepatient 2992 and/or insertion of the delivery cannula into the patient2992. The controller 2970 may control the communication module 2972 totransmit (e.g., wirelessly transmit) the report to an external computingsystem. In an embodiment where the communication module 2972 includes awireless transmitter, the controller 2970 may control the communicationmodule 2972 to wirelessly transmit the report. In some embodiments, thereport may be transmitted by the communication module 2972 to anexternal mobile device (e.g., the mobile device 110) and/or an externalcomputing device (e.g., the computing device 114).

FIGS. 30a and 30b illustrate an embodiment of an on-body injector 3000configured to detect and report contact between a housing of the on-bodyinjector 3000 and the patient. The on-body injector 3000 may includesome or all of the same components as the drug delivery system 800illustrated in FIGS. 14-16, including, for example, the housing 802having the exterior surface 816, the portion 828 of the exterior surface816 which is configured to face and/or contact the skin of the patientduring use of the on-body injector 3000, the controller 900, and thecommunication module 902. The portion 828 of the exterior surface 816may have an opening 3004 dimensioned to receive the distal end of thedelivery cannula 844.

The on-body injector 3000 may further include a sensor 3010 configuredto detect contact between the housing 802 and an object (e.g., the skinof a patient or the clothing of the patient). The sensor 3010 may becoupled to the controller 900 and configured to output a signal to thecontroller 900 indicative of contact with the object. According to oneembodiment, the sensor 3010 may include a first electrically conductivemember 3012 and second electrically conductive member 3014 coupled todifferent parts of the portion 828 of the exterior surface 816 of thehousing 802. In some embodiments, the first and second electricallyconductive members 3012, 3014 may each include an electricallyconductive adhesive (e.g., an electrically conductive gel adhesive pad).The first electrically conductive member 3012 may be spaced apart fromthe second electrically conductive member 3014 so that the first andsecond electrically conductive members 3012, 3014 do not physicallycontact each other.

When the portion 828 of the exterior surface 816 of the housing 802 ispressed against the skin of a patient, both the first and secondelectrically conductive members 3012, 3014 may contact the skin of thepatient. The skin of the patient may conduct electricity between thefirst and second electrically conductive members 3012, 3014.Consequently, a closed electrical circuit may be formed between thefirst and second electrically conductive members 3012, 3014 when boththe first and second electrically conductive members 3012, 3014 arepressed into contact with the skin of the patient. This closedelectrical circuit may output a signal to the controller 900.

In response to the signal from the sensor 3010, the controller 900 maydetermine that the housing 802 contacts the patient, and generate areport representative of contact between the housing 802 and the patientand/or insertion of the delivery cannula into the patient. Thecontroller 900 may control the communication module 902 to transmit(e.g., wirelessly transmit) the report to an external computing system.In an embodiment where the communication module 902 includes a wirelesstransmitter, the controller 900 may control the communication module 902to wirelessly transmit the report. In some embodiments, the report maybe transmitted by the communication module 902 to an external mobiledevice (e.g., the mobile device 110) and/or an external computing device(e.g., the computing device 114).

The foregoing methods and drug delivery systems describe locking out thedrug delivery device in response to various determinations regarding thecondition, the operational state, and/or the identity of the drugdelivery device, the medicament contained in the drug delivery device,and/or the user of the drug delivery device. A lock for achieving thisfunctionality may be coupled to the plunger assembly, the needle shield,and/or the actuator. In some embodiments, the lock may include a wallthat can be controlled to selectively abut spaces or notches in theplunger, needle shield, or actuator to limit movement of, respectively,the plunger, needle shield, or the actuator. In some embodiments, thelock may be coupled to and selectively activated by the controller ofthe drug delivery device.

In addition to monitoring and reporting conditions and/or operationalstates of drug delivery devices, the drug delivery systems and methodsof the present disclosure may include features that improve theirusability by patients, particularly patients who might have difficultygripping or handling drug delivery devices, such as elderly and disabledpatients. Described below with reference to FIGS. 31 and 32 is aremovable sterile barrier that, in addition to inhibiting thecontamination of an interior of a drug delivery device, provides ananti-roll functionality, helps patients grip and detach the removablesterile barrier from the drug delivery device, and optionally housesvarious electronic components including, for example, a controller, amemory, one or more sensors, and/or a communication module.

In particular, as illustrated in FIG. 31, a drug delivery system 3100 isprovided that includes a drug delivery device 3102. The drug deliverydevice 3102 may be in the form of an autoinjector, and thus configuredfor hand-held use and application against the skin of the patient. Thedrug delivery device 3102 may include some or all of the same componentsas the drug delivery devices described above in connection with FIGS. 9,12A, 12B, 13, and 17-29. The drug delivery device 3102 may include ahousing 3110 in which are disposed assemblies or structures thatintroduce a delivery cannula into a patient and that eject a drug ormedicament from a reservoir through the delivery cannula into thepatient. The drug delivery device 3102 may also include an actuator 3112disposed at a proximal end of the housing 3110 and configured to bedepressed by the patient to activate a drive to that causes a plunger todischarge the medicament from the reservoir through the delivery cannulainto the patient.

The drug delivery device 3102 may further include a removable sterilebarrier 3120 removably attached to a distal end of the housing 3110. Theremovable sterile barrier 3120 reduces the risk of contamination of thedelivery cannula and other elements within the housing 3110 prior to useof the drug delivery device 3102. The removable sterile barrier 3120 maybe formed by a tubular member 3122 and a cover member 3124 that coversan open end of the tubular member 3122. The tubular member 3122 and thecover member 3124 may be integrally formed as a single unitarystructure, or alternatively, formed as separate components which areadhered or mechanically interconnected to each other.

The tubular member 3122 may be disposed about (e.g., surround) thedistal end of the housing 3110 and/or a distal end of a delivery cannula(not illustrated), and may removably attach the removable sterilebarrier 3120 to the housing 3110. As shown in FIG. 32, the tubularmember 3122 may be assembled by fitting two interlocking and generallyC-shaped members 3128, 3130 over the distal end of the housing 3110. Insome embodiments, the removable sterile barrier 3120 may form aninterference or snap fit with the distal end of the housing 3110. Africtional force associated with the interference or snap fit may beovercome by manually pulling the removable sterile barrier 3120 in adistal direction away from a housing 3110. The interference or snap fitmay be formed by configuring an inner diameter of the tubular member3122 to be slightly smaller than an outer diameter of a distal end ofthe housing 3110. Alternatively, or additionally, the tubular member3122 may have a tearable or weakened member (not illustrated) thatconnects the tubular member 3122 to the distal end of the housing 3110and which can be broken or torn by the patient when pulling theremovable sterile barrier 3120 away from the housing 3110. The tubularmember 3122 may further include a plurality of outwardly protruding ribs3126 designed to help a patient grip the tubular member 3122 to detachit from the housing 3110. The ribs 3126 may be particularly useful toelderly and disabled patients who have below average gripping strength.

The cover member 3124 may be fixed to a distal end of the tubular member3122 and may completely cover an opening formed at the distal end of thetubular member 3122. A distal end surface 3132 of the cover member 3124may be planar such that the drug delivery device 3102 can be disposed onplanar surface in an upright configuration without falling over. Inalternative embodiments, the distal end surface 3132 of the cover member3124 may have a slight curvature to prevent a user from standing up thedrug delivery device 3102 on a planar surface. Also, an outer peripheralportion of the cover member 3124 may be wider than an outer peripheralportion of the tubular member 3122 such that a ledge or overhang 3134 isformed at the interface between the cover member 3124 and the tubularmember 3122. This ledge 3134 may help prevent a patient's fingers fromslipping over the cover member 3124 when trying to pull the removablesterile barrier 3120 off of the housing 3110.

Since the housing 3110 may have a circular cross section resulting in around exterior side surface, the drug delivery device 3102 may besusceptible to unintentionally rolling across a surface when it isplaced on its side. To inhibit or prevent the drug delivery device 3102from rolling across a surface when placed on its side, the tubularmember 3122 and/or the cover member 3124 may be formed with at least oneroll inhibiting exterior side surface. The at least one roll inhibitingexterior side surface may extend between proximal and distal ends of thetubular member 3122 and/or between proximal and distal ends of the covermember 3124. The at least one roll inhibiting exterior side surface ofthe tubular member 3122 and/or the cover member 3124 may be parallel toa longitudinal axis A of the drug delivery device 3102 and/orperpendicular to the distal end surface 3132 of the cover member 3124.

In the embodiment illustrated in FIGS. 31 and 32, the tubular member3122 has a triangular cross section formed by three planar exterior sidesurfaces 3140, 3142, and 3144, and the cover member 3124 has atriangular cross section formed by three planar exterior side surfaces3150, 3152, and 3154. The cross section at issue is the one which isperpendicular to the longitudinal axis A of the drug delivery device3102. Each of the planar exterior side surfaces 3140, 3142, 3144, 3150,3152, and 3154 is an example of a roll inhibiting exterior side surface.This is because each of the planar exterior side surfaces 3140, 3142,3144, 3150, 3152, and 3154 is configured to inhibit (e.g., prevent) theremovable sterile barrier 3120 and/or the drug delivery device 3102 fromrolling across a support surface when the respective planar exteriorside surface rests against the support surface.

As used herein, the term “planar” is hereby defined to mean flat orsubstantially flat. As shown in FIGS. 31 and 32, each of the planarexterior side surfaces 3140, 3142, 3144, 3150, 3152, and 3154 balloonsoutwardly and thus has a slight curvature. While the planar exteriorside surfaces 3140, 3142, 3144, 3150, 3152, and 3154 are not exactlyflat, they are nonetheless substantially flat and therefore areconsidered to be “planar” in accordance with principles of the presentdisclosure. In alternative embodiments, one or more of the planarexterior side surfaces 3140, 3142, 3144, 3150, 3152, and 3154 may beexactly flat such that it does not have any curvature. Regardless ofwhether the planar exterior side surfaces 3140, 3142, 3144, 3150, 3152,and 3154 have a flat configuration or a substantially flatconfiguration, the planar exterior side surfaces 3140, 3142, 3144, 3150,3152, and 3154 may have the ability to inhibit (e.g., prevent) rollingof the removable sterile barrier 3120 and/or the drug delivery device3102.

The anti-roll functionality of the removable sterile barrier 3120 may beachieved through a variety of different shapes and sizes of the tubularmember 3122 and/or the cover member 3124. In some embodiments, only thetubular member 3122, or only the cover member 3124, may have atriangular cross section. Other cross-sectional shapes of the tubularmember 3122 and/or the cover member 3124 are capable of preventing orinhibiting rolling including, but are not limited to, a hemisphere, asquare, a rectangle, a pentagon, hexagon, or any other polygonal shape.Also, the vertices or corners formed by the one or more planar exteriorside surfaces of the tubular member 3122 and/or the cover member 3124may be rounded so that the vertices or corners are not likely to causeinjury or pain to a patient while gripping the removable sterile barrier3120.

It should be noted that the particular shape of the removable sterilebarrier 3120 illustrated in FIGS. 31 and 32 is an aesthetic feature notdictated by function.

In an alternative embodiment, the drug delivery device 3102 may includea second removable sterile barrier, separate from the removable sterilebarrier 3120, that attaches directly to the reservoir and surrounds thedelivery cannula, similar to the removable sterile barrier 1750illustrated in FIG. 17. In such an embodiment, the removable sterilebarrier 3120 may cover and/or surround the second removable sterilebarrier.

Furthermore, various electronic components of the drug delivery device3102 may be housed (e.g., embedded) within the removable sterile barrier3120. For example, a controller, a memory, a processor (e.g., amicroprocessor), a communication module (e.g., a Bluetooth module, aBluetooth Low Energy module, etc.), a skin sensor, an orientationsensor, a fingerprint sensor, and/or a temperature sensor, configured ina manner similar to one of the embodiments discussed above in connectionwith FIGS. 9, 12A, 12B, 13, and 17-29, may be housed (e.g., embedded)within the removable sterile barrier 3120. In some embodiments, theremovable sterile barrier 3120 may be configured to include one or moreof the electronic elements 630-638 illustrated in FIG. 9.

The removable sterile barrier 3120 can be designed for single, one-timeuse, or for multiple uses. The embodiment of the removable sterilebarrier 3120 illustrated in FIG. 32 may be assembled by fitting each ofthe C-shaped members 3128, 3130 separately around the distal end of thehousing 3110 and then fixing the C-shaped members 3128, 3130 togetherwith an adhesive. After the user removes the removable sterile barrier3120 from the housing 3110, it may be difficult, if not impossible, tore-attach the removable sterile barrier 3120 to the housing 3110 (or thehousing of another drug delivery device), at least not without breakingapart the C-shaped members 3128, 3130 and then re-fitting, andre-adhering, them around the housing 3110. As a result, the removablesterile barrier 3120 illustrated in FIG. 32 may be disposable and onlyfor one-time use. In an alternative embodiment (not illustrated), theC-shaped members 3128, 3130 may be hinged together in a clam shellarrangement. In such an alternative embodiment, after removing theremovable sterile barrier 3120 from the housing 3110, it may be possibleto re-attach the removable sterile barrier 3120 to the housing 3110 (orthe housing of another drug delivery device) by opening the C-shapedmembers 3128, 3130 like a clam shell and then fitting them around thedistal end of the housing 3110. The non-hinged ends of the C-shapedmembers 3128, 3130 may include a locking mechanism (e.g., mating lockingtabs and/or slots) so that the C-shaped members 3128, 3130 can besecured to each other after they are secured around the housing 3110.Substantial cost savings may be realized by the re-usable configurationof the removable sterile barrier 3120 since the electronics onboard theremovable sterile barrier 3120 can be used more than once. In stillfurther embodiments, the removable sterile barrier 3120 may bemanufactured in one piece, and then installed axially onto the housing3110 of the drug delivery device 3102.

Removal of the removable sterile barrier 3120 from the housing 3110 maytrigger a mechanism that automatically turns on a communication module(e.g., a Bluetooth module, a Bluetooth Low Energy module, etc.), acontroller, and/or other electronic components embedded within theremovable sterile barrier 3120. In some embodiments, the mechanism maybe similar in construction and/or operation to the switch 632illustrated in FIG. 9. In other embodiments, such as the one illustratedin FIGS. 33 and 34, the removable sterile barrier 3120 may include aspring arm 3160 and a normally open momentary switch 3162 to achievethis functionality. The normally open momentary switch 3162 mayselectively provide an electrical connection between a battery and acontroller, a communication module, and/or other electronic componentsembedded in the removable sterile barrier 3120.

FIG. 33 illustrates a cross-sectional view of the removable sterilebarrier 3120 prior to its removal from the housing 3110 of the drugdelivery device 3102. The spring arm 3160 may have a first end 3164fixed to an inner wall 3166 of the removable sterile barrier 3120, asecond end 3168 moveable relative to the inner wall 3166 of theremovable sterile barrier 3120, and a deflectable body portion 3170 thatconnects the first and second ends 3164, 3168. The deflectable bodyportion 3170 may protrude inwardly from the inner wall 3166. As shown inFIG. 33, the deflectable body portion 3170 may have triangular shapewith its apex pointing inwardly away from the inner wall 3166. When theremovable sterile barrier 3120 is disposed about the housing 3110, thehousing 3110 may press against and deflect the deflectable body portion3170 of the spring arm 3160 so that the deflectable body portion 3170moves towards the inner wall 3166 and also downward in the distal axialdirection. As a result, the second end 3168 of the spring arm 3160 mayalso move downward in the distal axial direction, such that it no longercontacts and depresses the normally open momentary switch 3162.Accordingly, in this configuration, the normally open momentary switch3162 assumes an OFF position. When the normally open momentary switch3162 is in its OFF position, as shown in FIG. 33, the controller,communication module, and/or other electronic components may not besupplied with electrical power from the battery.

FIG. 34 illustrates the removable sterile barrier 3120 after it has beenremoved from the housing 3110 of the drug delivery device 3102. Theabsence of the housing 3110 allows the deflectable body portion 3170 ofthe spring arm 3160 to elastically return to its un-compressed, naturalshape. This causes the second end 3168 of the spring arm 3160 to moveupward in the proximal axial direction until it contacts and depressesthe normally open momentary switch 3162. By depressing the normally openmomentary switch 3162, the second end 3168 of the spring arm 3160 causesthe normally open momentary switch 3162 to assume its ON position. As aresult, a controller, a communication module, and/or other electroniccomponents embedded within the removable sterile barrier 3120 may beelectrically connected to, and powered by, a battery embedded within theremovable sterile barrier 3120. In some embodiments, the supplying thecontroller with electrical power may cause it to control thecommunication module to transmit a signal to an external computingdevice (e.g., a smartphone), via Bluetooth or Bluetooth Low Energycommunication, representative of removal of the removable sterilebarrier 3120 from the drug delivery device 3102.

During manufacturing, a delay may occur between the assembly of theremovable sterile barrier 3120 and its installation on the housing 3110of the drug delivery device 3102. During this delay, it may be desirableto prevent the second end 3168 of the spring arm 3160 from depressingthe normally open momentary switch 3162 and turning on the electronicsonboard the removable sterile barrier 3120. To address this concern, thedeflectable body portion 3170 of the spring arm 3160 may be twisted sothat the second end 3168 of the spring arm 3160 is not aligned with thenormally open momentary switch 3162. A pin (not illustrated) may holdsecond end 3168 of the spring arm 3160 in this non-alignedconfiguration. Later, when the removable sterile barrier 3120 is fitover the housing 3110, the housing 3110 may deflect the deflectable bodyportion 3170 of the spring arm 3160, thereby moving the second end 3168downward in the distal axial direction, in the manner discussed above.Accordingly, the second end 3168 will slip past the pin and thedeflectable body portion 3170 will naturally un-twist itself due to itselasticity. This motion may re-align the second end 3168 of the springarm 3160 with the normally open momentary switch 3162 so that when theremovable sterile barrier 3120 is later removed from the housing 3110,the second end 3168 of the spring arm 3160 will depress the normallyopen momentary switch 3162 (as seen FIG. 34).

The above description describes various systems and methods for use witha drug delivery device. It should be clear that the system, drugdelivery device or methods can further comprise use of a medicamentlisted below with the caveat that the following list should neither beconsidered to be all inclusive nor limiting. The medicament will becontained in a reservoir. In some instances, the reservoir is a primarycontainer that is either filled or pre-filled for treatment with themedicament. The primary container can be a cartridge or a pre-filledsyringe.

For example, the drug delivery device or more specifically the reservoirof the device may be filled with colony stimulating factors, such asgranulocyte colony-stimulating factor (G-CSF). Such G-CSF agentsinclude, but are not limited to, Neupogen® (filgrastim) and Neulasta®(pegfilgrastim). In various other embodiments, the drug delivery devicemay be used with various pharmaceutical products, such as anerythropoiesis stimulating agent (ESA), which may be in a liquid or alyophilized form. An ESA is any molecule that stimulates erythropoiesis,such as Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo®(epoetin delta), Mircera® (methyoxy polyethylene glycol-epoetin beta),Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon®(epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alfa),epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta),Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa,epoetin beta, epoetin zeta, epoetin theta, and epoetin delta, as well asthe molecules or variants or analogs thereof as disclosed in thefollowing patents or patent applications, each of which is hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,986,047; 6,583,272; 7,084,245; and 7,271,689;and PCT Publication Nos. WO 91/05867; WO 95/05465; WO 96/40772; WO00/24893; WO 01/81405; and WO 2007/136752.

An ESA can be an erythropoiesis stimulating protein. As used herein,“erythropoiesis stimulating protein” means any protein that directly orindirectly causes activation of the erythropoietin receptor, forexample, by binding to and causing dimerization of the receptor.Erythropoiesis stimulating proteins include erythropoietin and variants,analogs, or derivatives thereof that bind to and activate erythropoietinreceptor; antibodies that bind to erythropoietin receptor and activatethe receptor; or peptides that bind to and activate erythropoietinreceptor. Erythropoiesis stimulating proteins include, but are notlimited to, epoetin alfa, epoetin beta, epoetin delta, epoetin omega,epoetin iota, epoetin zeta, and analogs thereof, pegylatederythropoietin, carbamylated erythropoietin, mimetic peptides (includingEMP1/hematide), and mimetic antibodies. Exemplary erythropoiesisstimulating proteins include erythropoietin, darbepoetin, erythropoietinagonist variants, and peptides or antibodies that bind and activateerythropoietin receptor (and include compounds reported in U.S.Publication Nos. 2003/0215444 and 2006/0040858, the disclosures of eachof which is incorporated herein by reference in its entirety) as well aserythropoietin molecules or variants or analogs thereof as disclosed inthe following patents or patent applications, which are each hereinincorporated by reference in its entirety: U.S. Pat. Nos. 4,703,008;5,441,868; 5,547,933; 5,618,698; 5,621,080; 5,756,349; 5,767,078;5,773,569; 5,955,422; 5,830,851; 5,856,298; 5,986,047; 6,030,086;6,310,078; 6,391,633; 6,583,272; 6,586,398; 6,900,292; 6,750,369;7,030,226; 7,084,245; and 7,217,689; U.S. Publication Nos. 2002/0155998;2003/0077753; 2003/0082749; 2003/0143202; 2004/0009902; 2004/0071694;2004/0091961; 2004/0143857; 2004/0157293; 2004/0175379; 2004/0175824;2004/0229318; 2004/0248815; 2004/0266690; 2005/0019914; 2005/0026834;2005/0096461; 2005/0107297; 2005/0107591; 2005/0124045; 2005/0124564;2005/0137329; 2005/0142642; 2005/0143292; 2005/0153879; 2005/0158822;2005/0158832; 2005/0170457; 2005/0181359; 2005/0181482; 2005/0192211;2005/0202538; 2005/0227289; 2005/0244409; 2006/0088906; and2006/0111279; and PCT Publication Nos. WO 91/05867; WO 95/05465; WO99/66054; WO 00/24893; WO 01/81405; WO 00/61637; WO 01/36489; WO02/014356; WO 02/19963; WO 02/20034; WO 02/49673; WO 02/085940; WO03/029291; WO 2003/055526; WO 2003/084477; WO 2003/094858; WO2004/002417; WO 2004/002424; WO 2004/009627; WO 2004/024761; WO2004/033651; WO 2004/035603; WO 2004/043382; WO 2004/101600; WO2004/101606; WO 2004/101611; WO 2004/106373; WO 2004/018667; WO2005/001025; WO 2005/001136; WO 2005/021579; WO 2005/025606; WO2005/032460; WO 2005/051327; WO 2005/063808; WO 2005/063809; WO2005/070451; WO 2005/081687; WO 2005/084711; WO 2005/103076; WO2005/100403; WO 2005/092369; WO 2006/50959; WO 2006/02646; and WO2006/29094.

Examples of other pharmaceutical products for use with the device mayinclude, but are not limited to, antibodies such as Vectibix®(panitumumab), Xgeva™ (denosumab) and Prolia™ (denosamab); otherbiological agents such as Enbrel® (etanercept, TNF-receptor/Fc fusionprotein, TNF blocker), Neulasta® (pegfilgrastim, pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF), Neupogen® (filgrastim, G-CSF,hu-MetG-CSF), and Nplate® (romiplostim); small molecule drugs such asSensipar® (cinacalcet). The device may also be used with a therapeuticantibody, a polypeptide, a protein or other chemical, such as an iron,for example, ferumoxytol, iron dextrans, ferric glyconate, and ironsucrose. The pharmaceutical product may be in liquid form, orreconstituted from lyophilized form.

Among particular illustrative proteins are the specific proteins setforth below, including fusions, fragments, analogs, variants orderivatives thereof:

OPGL specific antibodies, peptibodies, and related proteins, and thelike (also referred to as RANKL specific antibodies, peptibodies and thelike), including fully humanized and human OPGL specific antibodies,particularly fully humanized monoclonal antibodies, including but notlimited to the antibodies described in PCT Publication No. WO 03/002713,which is incorporated herein in its entirety as to OPGL specificantibodies and antibody related proteins, particularly those having thesequences set forth therein, particularly, but not limited to, thosedenoted therein: 9H7; 18B2; 2D8; 2E11; 16E1; and 22B3, including theOPGL specific antibodies having either the light chain of SEQ ID NO:2 asset forth therein in FIG. 2 and/or the heavy chain of SEQ ID NO:4, asset forth therein in FIG. 4, each of which is individually andspecifically incorporated by reference herein in its entirety fully asdisclosed in the foregoing publication;

Myostatin binding proteins, peptibodies, and related proteins, and thelike, including myostatin specific peptibodies, particularly thosedescribed in U.S. Publication No. 2004/0181033 and PCT Publication No.WO 2004/058988, which are incorporated by reference herein in theirentirety particularly in parts pertinent to myostatin specificpeptibodies, including but not limited to peptibodies of the mTN8-19family, including those of SEQ ID NOS:305-351, including TN8-19-1through TN8-19-40, TN8-19 con1 and TN8-19 con2; peptibodies of the mL2family of SEQ ID NOS:357-383; the mL15 family of SEQ ID NOS:384-409; themL17 family of SEQ ID NOS:410-438; the mL20 family of SEQ IDNOS:439-446; the mL21 family of SEQ ID NOS:447-452; the mL24 family ofSEQ ID NOS:453-454; and those of SEQ ID NOS:615-631, each of which isindividually and specifically incorporated by reference herein in theirentirety fully as disclosed in the foregoing publication;

IL-4 receptor specific antibodies, peptibodies, and related proteins,and the like, particularly those that inhibit activities mediated bybinding of IL-4 and/or IL-13 to the receptor, including those describedin PCT Publication No. WO 2005/047331 or PCT Application No.PCT/US2004/37242 and in U.S. Publication No. 2005/112694, which areincorporated herein by reference in their entirety particularly in partspertinent to IL-4 receptor specific antibodies, particularly suchantibodies as are described therein, particularly, and withoutlimitation, those designated therein: L1H1; L1H2; L1H3; L1H4; L1H5;L1H6; L1H7; L1H8; L1H9; L1H10; L1H11; L2H1; L2H2; L2H3; L2H4; L2H5;L2H6; L2H7; L2H8; L2H9; L2H10; L2H11; L2H12; L2H13; L2H14; L3H1; L4H1;L5H1; L6H1, each of which is individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication;

Interleukin 1-receptor 1 (“IL1-R1”) specific antibodies, peptibodies,and related proteins, and the like, including but not limited to thosedescribed in U.S. Publication No. 2004/097712, which is incorporatedherein by reference in its entirety in parts pertinent to IL1-R1specific binding proteins, monoclonal antibodies in particular,especially, without limitation, those designated therein: 15CA, 26F5,27F2, 24E12, and 10H7, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe aforementioned publication;

Ang2 specific antibodies, peptibodies, and related proteins, and thelike, including but not limited to those described in PCT PublicationNo. WO 03/057134 and U.S. Publication No. 2003/0229023, each of which isincorporated herein by reference in its entirety particularly in partspertinent to Ang2 specific antibodies and peptibodies and the like,especially those of sequences described therein and including but notlimited to: L1(N); L1(N) WT; L1(N) 1K WT; 2×L1(N); 2×L1(N) WT; Con4 (N),Con4 (N) 1K WT, 2×Con4 (N) 1K; L1C; L1C 1K; 2×L1C; Con4C; Con4C 1K;2×Con4C 1K; Con4-L1 (N); Con4-L1C; TN-12-9 (N); C17 (N); TN8-8(N);TN8-14 (N); Con 1 (N), also including anti-Ang 2 antibodies andformulations such as those described in PCT Publication No. WO2003/030833 which is incorporated herein by reference in its entirety asto the same, particularly Ab526; Ab528; Ab531; Ab533; Ab535; Ab536;Ab537; Ab540; Ab543; Ab544; Ab545; Ab546; A551; Ab553; Ab555; Ab558;Ab559; Ab565; AbF1AbFD; AbFE; AbFJ; AbFK; AbG1D4; AbGC1E8; AbH1C12;Ab1A1; Ab1F; Ab1K, Ab1P; and Ab1P, in their various permutations asdescribed therein, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

NGF specific antibodies, peptibodies, and related proteins, and the likeincluding, in particular, but not limited to those described in U.S.Publication No. 2005/0074821 and U.S. Pat. No. 6,919,426, which areincorporated herein by reference in their entirety particularly as toNGF-specific antibodies and related proteins in this regard, includingin particular, but not limited to, the NGF-specific antibodies thereindesignated 4D4, 4G6, 6H9, 7H2, 14D10 and 14D11, each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing publication;

CD22 specific antibodies, peptibodies, and related proteins, and thelike, such as those described in U.S. Pat. No. 5,789,554, which isincorporated herein by reference in its entirety as to CD22 specificantibodies and related proteins, particularly human CD22 specificantibodies, such as but not limited to humanized and fully humanantibodies, including but not limited to humanized and fully humanmonoclonal antibodies, particularly including but not limited to humanCD22 specific IgG antibodies, such as, for instance, a dimer of ahuman-mouse monoclonal hLL2 gamma-chain disulfide linked to ahuman-mouse monoclonal hLL2 kappa-chain, including, but limited to, forexample, the human CD22 specific fully humanized antibody inEpratuzumab, CAS registry number 501423-23-0;

IGF-1 receptor specific antibodies, peptibodies, and related proteins,and the like, such as those described in PCT Publication No. WO06/069202, which is incorporated herein by reference in its entirety asto IGF-1 receptor specific antibodies and related proteins, includingbut not limited to the IGF-1 specific antibodies therein designatedL1H1, L2H2, L3H3, L4H4, L5H5, L6H6, L7H7, L8H8, L9H9, L10H10, L11H11,L12H12, L13H13, L14H14, L15H15, L16H16, L17H17, L18H18, L19H19, L20H20,L21H21, L22H22, L23H23, L24H24, L25H25, L26H26, L27H27, L28H28, L29H29,L30H30, L31H31, L32H32, L33H33, L34H34, L35H35, L36H36, L37H37, L38H38,L39H39, L40H40, L41H41, L42H42, L43H43, L44H44, L45H45, L46H46, L47H47,L48H48, L49H49, L50H50, L51H51, L52H52, and IGF-1R-binding fragments andderivatives thereof, each of which is individually and specificallyincorporated by reference herein in its entirety fully as disclosed inthe foregoing publication;

Also among non-limiting examples of anti-IGF-1R antibodies for use inthe methods and compositions of the present invention are each and allof those described in:

(i) U.S. Publication No. 2006/0040358 (published Feb. 23, 2006),2005/0008642 (published Jan. 13, 2005), 2004/0228859 (published Nov. 18,2004), including but not limited to, for instance, antibody 1A (DSMZDeposit No. DSM ACC 2586), antibody 8 (DSMZ Deposit No. DSM ACC 2589),antibody 23 (DSMZ Deposit No. DSM ACC 2588) and antibody 18 as describedtherein;

(ii) PCT Publication No. WO 06/138729 (published Dec. 28, 2006) and WO05/016970 (published Feb. 24, 2005), and Lu et al. (2004), J. Biol.Chem. 279:2856-2865, including but not limited to antibodies 2F8, A12,and IMC-A12 as described therein;

(iii) PCT Publication No. WO 07/012614 (published Feb. 1, 2007), WO07/000328 (published Jan. 4, 2007), WO 06/013472 (published Feb. 9,2006), WO 05/058967 (published Jun. 30, 2005), and WO 03/059951(published Jul. 24, 2003);

(iv) U.S. Publication No. 2005/0084906 (published Apr. 21, 2005),including but not limited to antibody 7C10, chimaeric antibody C7C10,antibody h7C10, antibody 7H2M, chimaeric antibody *7C10, antibody GM607, humanized antibody 7C10 version 1, humanized antibody 7C10 version2, humanized antibody 7C10 version 3, and antibody 7H2HM, as describedtherein;

(v) U.S. Publication Nos. 2005/0249728 (published Nov. 10, 2005),2005/0186203 (published Aug. 25, 2005), 2004/0265307 (published Dec. 30,2004), and 2003/0235582 (published Dec. 25, 2003) and Maloney et al.(2003), Cancer Res. 63:5073-5083, including but not limited to antibodyEM164, resurfaced EM164, humanized EM164, huEM164 v1.0, huEM164 v1.1,huEM164 v1.2, and huEM164 v1.3 as described therein;

(vi) U.S. Pat. No. 7,037,498 (issued May 2, 2006), U.S. Publication Nos.2005/0244408 (published Nov. 30, 2005) and 2004/0086503 (published May6, 2004), and Cohen, et al. (2005), Clinical Cancer Res. 11:2063-2073,e.g., antibody CP-751,871, including but not limited to each of theantibodies produced by the hybridomas having the ATCC accession numbersPTA-2792, PTA-2788, PTA-2790, PTA-2791, PTA-2789, PTA-2793, andantibodies 2.12.1, 2.13.2, 2.14.3, 3.1.1, 4.9.2, and 4.17.3, asdescribed therein;

(vii) U.S. Publication Nos. 2005/0136063 (published Jun. 23, 2005) and2004/0018191 (published Jan. 29, 2004), including but not limited toantibody 19D12 and an antibody comprising a heavy chain encoded by apolynucleotide in plasmid 15H12/19D12 HCA (γ4), deposited at the ATCCunder number PTA-5214, and a light chain encoded by a polynucleotide inplasmid 15H12/19D12 LCF (κ), deposited at the ATCC under numberPTA-5220, as described therein; and

(viii) U.S. Publication No. 2004/0202655 (published Oct. 14, 2004),including but not limited to antibodies PINT-6A1, PINT-7A2, PINT-7A4,PINT-7A5, PINT-7A6, PINT-8A1, PINT-9A2, PINT-11A1, PINT-11A2, PINT-11A3,PINT-11A4, PINT-11A5, PINT-11A7, PINT-11A12, PINT-12A1, PINT-12A2,PINT-12A3, PINT-12A4, and PINT-12A5, as described therein; each and allof which are herein incorporated by reference in their entireties,particularly as to the aforementioned antibodies, peptibodies, andrelated proteins and the like that target IGF-1 receptors;

B-7 related protein 1 specific antibodies, peptibodies, related proteinsand the like (“B7RP-1,” also is referred to in the literature as B7H2,ICOSL, B7h, and CD275), particularly B7RP-specific fully humanmonoclonal IgG2 antibodies, particularly fully human IgG2 monoclonalantibody that binds an epitope in the first immunoglobulin-like domainof B7RP-1, especially those that inhibit the interaction of B7RP-1 withits natural receptor, ICOS, on activated T cells in particular,especially, in all of the foregoing regards, those disclosed in U.S.Publication No. 2008/0166352 and PCT Publication No. WO 07/011941, whichare incorporated herein by reference in their entireties as to suchantibodies and related proteins, including but not limited to antibodiesdesignated therein as follow: 16H (having light chain variable and heavychain variable sequences SEQ ID NO:1 and SEQ ID NO:7 respectivelytherein); 5D (having light chain variable and heavy chain variablesequences SEQ ID NO:2 and SEQ ID NO:9 respectively therein); 2H (havinglight chain variable and heavy chain variable sequences SEQ ID NO:3 andSEQ ID NO:10 respectively therein); 43H (having light chain variable andheavy chain variable sequences SEQ ID NO:6 and SEQ ID NO:14 respectivelytherein); 41H (having light chain variable and heavy chain variablesequences SEQ ID NO:5 and SEQ ID NO:13 respectively therein); and 15H(having light chain variable and heavy chain variable sequences SEQ IDNO:4 and SEQ ID NO:12 respectively therein), each of which isindividually and specifically incorporated by reference herein in itsentirety fully as disclosed in the foregoing publication;

IL-15 specific antibodies, peptibodies, and related proteins, and thelike, such as, in particular, humanized monoclonal antibodies,particularly antibodies such as those disclosed in U.S. Publication Nos.2003/0138421; 2003/023586; and 2004/0071702; and U.S. Pat. No.7,153,507, each of which is incorporated herein by reference in itsentirety as to IL-15 specific antibodies and related proteins, includingpeptibodies, including particularly, for instance, but not limited to,HuMax IL-15 antibodies and related proteins, such as, for instance,146B7;

IFN gamma specific antibodies, peptibodies, and related proteins and thelike, especially human IFN gamma specific antibodies, particularly fullyhuman anti-IFN gamma antibodies, such as, for instance, those describedin U.S. Publication No. 2005/0004353, which is incorporated herein byreference in its entirety as to IFN gamma specific antibodies,particularly, for example, the antibodies therein designated 1118;1118*; 1119; 1121; and 1121*. The entire sequences of the heavy andlight chains of each of these antibodies, as well as the sequences oftheir heavy and light chain variable regions and complementaritydetermining regions, are each individually and specifically incorporatedby reference herein in its entirety fully as disclosed in the foregoingpublication and in Thakur et al. (1999), Mol. Immunol. 36:1107-1115. Inaddition, description of the properties of these antibodies provided inthe foregoing publication is also incorporated by reference herein inits entirety. Specific antibodies include those having the heavy chainof SEQ ID NO:17 and the light chain of SEQ ID NO:18; those having theheavy chain variable region of SEQ ID NO:6 and the light chain variableregion of SEQ ID NO:8; those having the heavy chain of SEQ ID NO:19 andthe light chain of SEQ ID NO:20; those having the heavy chain variableregion of SEQ ID NO:10 and the light chain variable region of SEQ IDNO:12; those having the heavy chain of SEQ ID NO:32 and the light chainof SEQ ID NO:20; those having the heavy chain variable region of SEQ IDNO:30 and the light chain variable region of SEQ ID NO:12; those havingthe heavy chain sequence of SEQ ID NO:21 and the light chain sequence ofSEQ ID NO:22; those having the heavy chain variable region of SEQ IDNO:14 and the light chain variable region of SEQ ID NO:16; those havingthe heavy chain of SEQ ID NO:21 and the light chain of SEQ ID NO:33; andthose having the heavy chain variable region of SEQ ID NO:14 and thelight chain variable region of SEQ ID NO:31, as disclosed in theforegoing publication. A specific antibody contemplated is antibody 1119as disclosed in the foregoing U.S. publication and having a completeheavy chain of SEQ ID NO:17 as disclosed therein and having a completelight chain of SEQ ID NO:18 as disclosed therein;

TALL-1 specific antibodies, peptibodies, and the related proteins, andthe like, and other TALL specific binding proteins, such as thosedescribed in U.S. Publication Nos. 2003/0195156 and 2006/0135431, eachof which is incorporated herein by reference in its entirety as toTALL-1 binding proteins, particularly the molecules of Tables 4 and 5B,each of which is individually and specifically incorporated by referenceherein in its entirety fully as disclosed in the foregoing publications;

Parathyroid hormone (“PTH”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,756,480, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind PTH;

Thrombopoietin receptor (“TPO-R”) specific antibodies, peptibodies, andrelated proteins, and the like, such as those described in U.S. Pat. No.6,835,809, which is herein incorporated by reference in its entirety,particularly in parts pertinent to proteins that bind TPO-R;

Hepatocyte growth factor (“HGF”) specific antibodies, peptibodies, andrelated proteins, and the like, including those that target theHGF/SF:cMet axis (HGF/SF:c-Met), such as the fully human monoclonalantibodies that neutralize hepatocyte growth factor/scatter (HGF/SF)described in U.S. Publication No. 2005/0118643 and PCT Publication No.WO 2005/017107, huL2G7 described in U.S. Pat. No. 7,220,410 and OA-5d5described in U.S. Pat. Nos. 5,686,292 and 6,468,529 and in PCTPublication No. WO 96/38557, each of which is incorporated herein byreference in its entirety, particularly in parts pertinent to proteinsthat bind HGF;

TRAIL-R2 specific antibodies, peptibodies, related proteins and thelike, such as those described in U.S. Pat. No. 7,521,048, which isherein incorporated by reference in its entirety, particularly in partspertinent to proteins that bind TRAIL-R2;

Activin A specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. PublicationNo. 2009/0234106, which is herein incorporated by reference in itsentirety, particularly in parts pertinent to proteins that bind ActivinA;

TGF-beta specific antibodies, peptibodies, related proteins, and thelike, including but not limited to those described in U.S. Pat. No.6,803,453 and U.S. Publication No. 2007/0110747, each of which is hereinincorporated by reference in its entirety, particularly in partspertinent to proteins that bind TGF-beta;

Amyloid-beta protein specific antibodies, peptibodies, related proteins,and the like, including but not limited to those described in PCTPublication No. WO 2006/081171, which is herein incorporated byreference in its entirety, particularly in parts pertinent to proteinsthat bind amyloid-beta proteins. One antibody contemplated is anantibody having a heavy chain variable region comprising SEQ ID NO:8 anda light chain variable region having SEQ ID NO:6 as disclosed in theforegoing publication;

c-Kit specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2007/0253951, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind c-Kit and/or otherstem cell factor receptors;

OX40L specific antibodies, peptibodies, related proteins, and the like,including but not limited to those described in U.S. Publication No.2006/0002929, which is incorporated herein by reference in its entirety,particularly in parts pertinent to proteins that bind OX40L and/or otherligands of the OX40 receptor; and

Other exemplary proteins, including Activase® (alteplase, tPA); Aranesp®(darbepoetin alfa); Epogen® (epoetin alfa, or erythropoietin); GLP-1,Avonex® (interferon beta-1a); Bexxar® (tositumomab, anti-CD22 monoclonalantibody); Betaseron® (interferon-beta); Campath® (alemtuzumab,anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade®(bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokinereceptor mAb); Enbrel® (etanercept, TNF-receptor/Fc fusion protein, TNFblocker); Eprex® (epoetin alfa); Erbitux® (cetuximab,anti-EGFR/HER1/c-ErbB-1); Genotropin® (somatropin, Human GrowthHormone); Herceptin® (trastuzumab, anti-HER2/neu (erbB2) receptor mAb);Humatrope® (somatropin, Human Growth Hormone); Humira® (adalimumab);insulin in solution; Infergen® (interferon alfacon-1); Natrecor®(nesiritide; recombinant human B-type natriuretic peptide (hBNP);Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide®(epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab,anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin);Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™(eculizumab); pexelizumab (anti-C5 complement); Numax® (MEDI-524);Lucentis® (ranibizumab); Panorex® (17-1A, edrecolomab); Trabio®(lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4);Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (visilizumab); cantuzumabmertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega®(oprelvekin, human interleukin-11); Neulasta® (pegylated filgastrim,pegylated G-CSF, pegylated hu-Met-G-CSF); Neupogen® (filgrastim, G-CSF,hu-MetG-CSF); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonalantibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNFαmonoclonal antibody); Reopro® (abciximab, anti-GP 1Ib/Ilia receptormonoclonal antibody); Actemra® (anti-IL6 Receptor mAb); Avastin®(bevacizumab), HuMax-CD4 (zanolimumab); Rituxan® (rituximab, anti-CD20mAb); Tarceva® (erlotinib); Roferon-A®-(interferon alfa-2a); Simulect®(basiliximab); Prexige® (lumiracoxib); Synagis® (palivizumab); 146B7-CHO(anti-IL15 antibody, see U.S. Pat. No. 7,153,507); Tysabri®(natalizumab, anti-α4integrin mAb); Valortim® (MDX-1303, anti-B.anthracis protective antigen mAb); ABthrax™; Vectibix® (panitumumab);Xolair® (omalizumab); ETI211 (anti-MRSA mAb); IL-1 trap (the Fc portionof human IgG1 and the extracellular domains of both IL-1 receptorcomponents (the Type I receptor and receptor accessory protein)); VEGFtrap (Ig domains of VEGFR1 fused to IgG1 Fc); Zenapax® (daclizumab);Zenapax® (daclizumab, anti-IL-2Rα mAb); Zevalin® (ibritumomab tiuxetan);Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonalantibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3/huFcfusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFαmAb); HGS-ETR1 (mapatumumab; human anti-TRAIL Receptor-1 mAb);HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab);M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab,anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAb; anti-C. difficileToxin A and Toxin B C mAbs MDX-066 (CDA-1) and MDX-1388); anti-CD22dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC);anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333(anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-CriptomAb; anti-CTGF Idiopathic Pulmonary Fibrosis Phase I Fibrogen (FG-3019);anti-CTLA4 mAb; anti-eotaxin1 mAb (CAT-213); anti-FGF8 mAb;anti-ganglioside GD2 mAb; anti-ganglioside GM2 mAb; anti-GDF-8 human mAb(MYO-029); anti-GM-CSF Receptor mAb (CAM-3001); anti-HepC mAb (HuMaxHepC); anti-IFNα mAb (MEDI-545, MDX-1103); anti-IGF1R mAb; anti-IGF-1RmAb (HuMax-Inflam); anti-IL12 mAb (ABT-874); anti-IL12/IL23 mAb (CNTO1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5Receptor mAb; anti-integrin receptors mAb (MDX-018, CNTO 95); anti-IP10Ulcerative Colitis mAb (MDX-1100); anti-LLY antibody; BMS-66513;anti-Mannose Receptor/hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38conjugate (CAT-5001); anti-PD1mAb (MDX-1106 (ONO-4538)); anti-PDGFRαantibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL Receptor-2 humanmAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR/Flt-1 mAb; anti-ZP3 mAb(HuMax-ZP3); NVS Antibody #1; and NVS Antibody #2.

Also included can be a sclerostin antibody, such as but not limited toromosozumab, blosozumab, or BPS 804 (Novartis). Further included can betherapeutics such as rilotumumab, bixalomer, trebananib, ganitumab,conatumumab, motesanib diphosphate, brodalumab, vidupiprant,panitumumab, denosumab, NPLATE, PROLIA, VECTIBIX or XGEVA. Additionally,included in the device can be a monoclonal antibody (IgG) that bindshuman Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), e.g. U.S.Pat. No. 8,030,547, U.S. Publication No. 2013/0064825, WO2008/057457,WO2008/057458, WO2008/057459, WO2008/063382, WO2008/133647,WO2009/100297, WO2009/100318, WO2011/037791, WO2011/053759,WO2011/053783, WO2008/125623, WO2011/072263, WO2009/055783,WO2012/0544438, WO2010/029513, WO2011/111007, WO2010/077854,WO2012/088313, WO2012/101251, WO2012/101252, WO2012/101253,WO2012/109530, and WO2001/031007.

Also included can be talimogene laherparepvec or another oncolytic HSVfor the treatment of melanoma or other cancers. Examples of oncolyticHSV include, but are not limited to talimogene laherparepvec (U.S. Pat.Nos. 7,223,593 and 7,537,924); OncoVEXGALV/CD (U.S. Pat. No. 7,981,669);OrienX010 (Lei et al. (2013), World J. Gastroenterol., 19:5138-5143);G207, 1716; NV1020; NV12023; NV1034 and NV1042 (Vargehes et al. (2002),Cancer Gene Ther., 9(12):967-978).

Also included are TIMPs. TIMPs are endogenous tissue inhibitors ofmetalloproteinases (TIMPs) and are important in many natural processes.TIMP-3 is expressed by various cells or and is present in theextracellular matrix; it inhibits all the major cartilage-degradingmetalloproteases, and may play a role in role in many degradativediseases of connective tissue, including rheumatoid arthritis andosteoarthritis, as well as in cancer and cardiovascular conditions. Theamino acid sequence of TIMP-3, and the nucleic acid sequence of a DNAthat encodes TIMP-3, are disclosed in U.S. Pat. No. 6,562,596, issuedMay 13, 2003, the disclosure of which is incorporated by referenceherein. Description of TIMP mutations can be found in U.S. PublicationNo. 2014/0274874 and PCT Publication No. WO 2014/152012.

Also included are antagonistic antibodies for human calcitoningene-related peptide (CGRP) receptor and bispecific antibody moleculethat target the CGRP receptor and other headache targets. Furtherinformation concerning these molecules can be found in PCT ApplicationNo. WO 2010/075238.

Additionally, a bispecific T cell engager antibody (BiTe), e.g.Blinotumomab can be used in the device. Alternatively, included can bean APJ large molecule agonist e.g., apelin or analogues thereof in thedevice. Information relating to such molecules can be found in PCTPublication No. WO 2014/099984.

In certain embodiments, the medicament comprises a therapeuticallyeffective amount of an anti-thymic stromal lymphopoietin (TSLP) or TSLPreceptor antibody. Examples of anti-TSLP antibodies that may be used insuch embodiments include, but are not limited to, those described inU.S. Pat. Nos. 7,982,016, and 8,232,372, and U.S. Publication No.2009/0186022. Examples of anti-TSLP receptor antibodies include, but arenot limited to, those described in U.S. Pat. No. 8,101,182. Inparticularly preferred embodiments, the medicament comprises atherapeutically effective amount of the anti-TSLP antibody designated asA5 within U.S. Pat. No. 7,982,016.

It should be noted that the configurations of the various embodiments ofthe drug delivery devices and drug delivery systems described herein areillustrative only. Although only a few embodiments of the of the drugdelivery devices and drug delivery systems have been described in detailin this disclosure, those skilled in the art who review this disclosurewill readily appreciate that many modifications are possible (e.g.,variations in sizes, dimensions, structures, shapes and proportions ofthe various elements, values of parameters, mounting arrangements, useof materials, orientations, etc.) without materially departing from thenovel teachings and advantages of the subject matter of this disclosure.For example, any combination of one or more of the sensors and sensorsystems described herein may be incorporated into one or more of thedrug delivery systems and drug delivery devices described herein. Also,the order or sequence of any process or method steps described hereinmay be varied or re-sequenced, in any combination, according toalternative embodiments. Furthermore, any combination of one or more ofthe elements of one or more of the claims set forth at the end of thisdisclosure is possible.

Although the preceding text sets forth a detailed description ofdifferent embodiments of the invention, it should be understood that thelegal scope of the invention is defined by the words of the claims setforth at the end of this patent. The detailed description is to beconstrued as exemplary only and does not describe every possibleembodiment of the invention because describing every possible embodimentwould be impractical, if not impossible. Numerous alternativeembodiments could be implemented, using either current technology ortechnology developed after the filing date of this patent, that wouldstill fall within the scope of the claims defining the invention.

It should also be understood that, unless a term is expressly defined inthis patent using the sentence “As used herein, the term ‘ ’ is herebydefined to mean . . . ” or a similar sentence, there is no intent tolimit the meaning of that term, either expressly or by implication,beyond its plain or ordinary meaning, and such term should not beinterpreted to be limited in scope based on any statement made in anysection of this patent (other than the language of the claims). To theextent that any term recited in the claims at the end of this patent isreferred to in this patent in a manner consistent with a single meaning,that is done for sake of clarity only so as to not confuse the reader,and it is not intended that such claim term be limited, by implicationor otherwise, to that single meaning. Finally, unless a claim element isdefined by reciting the word “means” and a function without the recitalof any structure, it is not intended that the scope of any claim elementbe interpreted based on the application of 35 U.S.C. §112, sixthparagraph.

1. A drug delivery system comprising: a drug delivery device comprisinga reservoir and a delivery cannula having a proximal end in fluidcommunication with the reservoir and a distal end to be received withina patient; one or more sensors coupled to the drug delivery device; awireless transmitter; and a controller coupled to the one or moresensors and the wireless transmitter, the controller being configuredto: use the one or more sensors to determine a condition or anoperational state of the drug delivery device, and control the wirelesstransmitter to wirelessly transmit one or more reports representative ofthe condition or the operational state of the drug delivery device. 2.The drug delivery system of claim 1, wherein: the drug delivery devicecomprises a removable sterile barrier disposed about the distal end ofthe delivery cannula; the one or more sensors are configured to detectmovement of the removable sterile barrier; and the controller isconfigured to: use the one or more sensors to determine if the removablesterile barrier has been removed from the distal end of the deliverycannula, and control the wireless transmitter to wirelessly transmit areport representative of removal of the removable sterile barrier if theremovable sterile barrier has been removed from the distal end of thedelivery cannula. 3-13. (canceled)
 14. The drug delivery system of claim1, the drug delivery device comprising: a housing containing thereservoir and the delivery cannula; and a removable sterile barrierdisposed about a distal end of the housing, the removable sterilebarrier having at least one roll inhibiting exterior side surface. 15.The drug delivery system of claim 14, at least a portion of theremovable sterile barrier having a triangular cross section.
 16. Thedrug delivery system of claim 14, the removable sterile barrier having aplanar distal end surface, the at least one roll inhibiting exteriorside surface being perpendicular to the planar distal end surface. 17.The drug delivery system of claim 14, the removable sterile barrierincluding a cover member and a tubular member, the cover member coveringan open end of the tubular member, and the tubular member including aplurality of outwardly protruding ribs to be gripped by the patient whenremoving the removable sterile barrier from the housing.
 18. The drugdelivery stem of claim 14, the controller and the wireless transmitterbeing housed within the removable sterile barrier.
 19. The drug deliverysystem of claim 1, wherein the reservoir comprises a medicament.
 20. Thedrug delivery system of claim 19, the medicament being selected from thegroup consisting of: TNF inhibitors, antibodies to the calcitoningene-related peptide receptor, granulocyte colony stimulating factors,erythropoiesis stimulating agents, apelin receptor agonists, antibodiesto proprotein convertase subtilisin/kexin Type 9 (PCSK9), and tissueinhibitors of metalloproteinases.
 21. A drug delivery system comprising:a drug delivery device comprising a reservoir, a delivery cannula havinga proximal end in fluid communication with the reservoir and a distalend to be received within a patient, and a removable sterile barrierdisposed about the distal end of the delivery cannula; a first sensorconfigured to detect movement of the removable sterile barrier; awireless transmitter; and a controller coupled to the first sensor andthe wireless transmitter, the controller being configured to: use thefirst sensor to determine if the removable sterile barrier has beenremoved from the distal end of the delivery cannula, and control thewireless transmitter to wirelessly transmit a report representative ofremoval of the removable sterile barrier if the removable sterilebarrier has been removed from the distal end of the delivery cannula.22. The drug delivery system of claim 21, comprising: the drug deliverydevice comprising an actuator configured to trigger the drug deliverydevice; a second sensor configured to detect movement of the actuator;and the controller being coupled to the second sensor and configured to:use the second sensor to determine if the actuator has been used totrigger the drug delivery device, and control the wireless transmitterto wirelessly transmit a report representative of the triggering thedrug delivery device if the actuator has been used.
 23. The drugdelivery system of claim 22, comprising: the drug delivery devicecomprising a needle shield moveable relative to the distal end of thedelivery cannula between a proximal position and a distal position; athird sensor and a fourth sensor each being configured to detectmovement of the needle shield; and the controller being coupled to thethird sensor and configured to: use the third sensor to determine if theneedle shield has been moved relative to the distal end of the deliverycannula, control the wireless transmitter to wirelessly transmit areport representative of insertion of the distal end of the deliverycannula into the patient if the needle shield has been moved relative tothe distal end of the delivery cannula, use the fourth sensor todetermine if the needle shield is disposed about the distal end of thedelivery cannula, and control the wireless transmitter to wirelesslytransmit a report representative of a completion of a delivery of amedicament from the reservoir to the patient if the needle shield isdisposed about the distal end of the delivery cannula after having beenmoved from the proximal position to the distal position.
 24. The drugdelivery system of claim 21, comprising: the drug delivery devicecomprising a needle shield moveable relative to the distal end of thedelivery cannula between a proximal position and a distal position; asecond sensor configured to detect movement of the needle shield; andthe controller being coupled to the second sensor and configured to: usethe second sensor to determine if the needle shield has been movedrelative to the distal end of the delivery cannula, and control thewireless transmitter to wirelessly transmit a report representative ofinsertion of the distal end of the delivery cannula into the patient ifthe needle shield has been moved relative to the distal end of thedelivery cannula.
 25. The drug delivery system of claim 21, comprising:a needle shield moveable relative to the distal end of the deliverycannula between a proximal position and a distal position; a secondsensor configured to detect movement of the needle shield; and thecontroller being coupled to the second sensor and configured to: use thesecond sensor to determine if the needle shield is disposed about thedistal end of the delivery cannula, and control the wireless transmitterto wirelessly transmit a report representative of a completion of adelivery of a medicament from the reservoir to the patient if the needleshield is disposed about the distal end of the delivery cannula afterhaving been moved from the proximal position to the distal position. 26.The drug delivery system of claim 22, comprising: the drug deliverydevice comprising a needle shield moveable relative to the distal end ofthe delivery cannula; a third sensor configured to detect movement ofthe needle shield; and the controller being coupled to the third sensorand configured to: use the third sensor to determine if the needleshield has been moved relative to the distal end of the deliverycannula, and control the wireless transmitter to wirelessly transmit areport representative of insertion of the distal end of the deliverycannula into the patient if the needle shield has been moved relative tothe distal end of the delivery cannula.
 27. The drug delivery system ofclaim 22, comprising: the drug delivery device comprising a needleshield moveable relative to the distal end of the delivery cannula; athird sensor configured to detect movement of the needle shield; and thecontroller being coupled to the third sensor and configured to: use thethird sensor to determine if the needle shield is disposed about thedistal end of the delivery cannula, and control the wireless transmitterto wirelessly transmit a report representative of a completion of adelivery of a medicament from the reservoir to the patient if the needleshield is disposed about the distal end of the delivery cannula.
 28. Thedrug delivery system of claim 24, comprising: the controller beingconfigured to: use the second sensor to determine if the needle shieldis disposed about the distal end of the delivery cannula, and controlthe wireless transmitter to wirelessly transmit a report representativeof a completion of a delivery of a medicament from the reservoir to thepatient if the needle shield is disposed about the distal end of thedelivery cannula after having been moved from the proximal position tothe distal position.
 29. The drug delivery system of claim 21, whereinthe first sensor, the wireless transmitter, and the controller areembedded in the removable sterile barrier.
 30. The drug delivery systemof claim 21, wherein the controller is configured to limit delivery of amedicament contained in the reservoir if it is determined that theremovable sterile barrier has been prematurely removed.
 31. The drugdelivery system of claim 30, wherein the controller is configured todetermine if the reservoir has been replaced if it is determined thatthe removable sterile barrier has been prematurely removed, and topermit delivery if it is determined that the reservoir has beenreplaced.
 32. The drug delivery system of claim 21, wherein thecontroller is configured to limit delivery of a medicament contained inthe reservoir unless it is determined that the removable sterile barrierhas been properly removed.
 33. The drug delivery system of claim 21,wherein the controller is configured to use the sterility sensor todetermine if the removable sterile barrier has been removed from thedistal end of the delivery cannula and to determine if a time period haselapsed, and to control the wireless transmitter to transmit a report ifthe removable sterile barrier has been removed from the distal end ofthe delivery cannula and the time period has elapsed.
 34. The drugdelivery system of claim 33, wherein the drug delivery device comprisesa lock and the controller is coupled to the lock, the controller beingconfigured to actuate the lock if the removable sterile barrier has beenremoved from the distal end of the delivery cannula and the time periodhas elapsed.
 35. The drug delivery system of claim 21, wherein thereservoir comprises a medicament.
 36. The drug delivery system of claim35, the medicament being selected from the group consisting of: TNFinhibitors, antibodies to the calcitonin gene-related peptide receptor,granulocyte colony stimulating factors, erythropoiesis stimulatingagents, apelin receptor agonists, antibodies to proprotein convertasesubtilisin/kexin Type 9 (PCSK9), and tissue inhibitors ofmetalloproteinases. 37-121. (canceled)
 122. A method for use with a drugdelivery device comprising a reservoir, a delivery cannula having aproximal end in fluid communication with the reservoir and a distal endto be received within a patient, and a removable sterile barrierdisposed about the second end of the delivery cannula, the methodcomprising: determining if the removable sterile barrier has beenremoved from the distal end of the delivery cannula; and transmitting areport representative of the removal of the removable sterile barrier ifthe removable sterile barrier has been removed from the distal end ofthe delivery cannula.
 123. The method of claim 122, further comprising:receiving the report representative of the removal of the removablesterile barrier at a first computing device; and transmitting the reportfrom the first computing device to a second computing device.
 124. Themethod of claim 122, further comprising: limiting delivery of amedicament contained in the reservoir if it is determined that theremovable sterile barrier has been removed.
 125. The method of claim122, further comprising: determining if the reservoir has been replacedif it is determined that the removable sterile barrier has been removed;and permitting delivery of a medicament contained in the reservoir if itis determined that the reservoir has been replaced.
 126. The method ofclaim 122, further comprising: limiting delivery of a medicamentcontained in the reservoir until it is determined that the removablesterile barrier has been removed.
 127. The method of claim 122, furthercomprising: determining if a time period has elapsed following removalof the sterile barrier; and transmitting a report if the removablesterile barrier has been removed from the distal end of the deliverycannula and the time period has elapsed.
 128. The method of claim 127,further comprising: locking the drug delivery device if the removablesterile barrier has been removed from the distal end of the deliverycannula and the time period has elapsed.
 129. The method of claim 122,wherein the reservoir comprises a medicament.
 130. The method of claim129, wherein the medicament is selected from the group consisting of:TNF inhibitors, antibodies to the calcitonin gene-related peptidereceptor, granulocyte colony stimulating factors, erythropoiesisstimulating agents, apelin receptor agonists, antibodies to proproteinconvertase subtilisin/kexin Type 9 (PCSK9), and tissue inhibitors ofmetalloproteinases.